The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index; none of the 50 sources its claims cite is checked for support yet.
Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation
Open accessAbstract
How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Neuronal differentiation from human NPCs is marked by shutting off aerobic glycolysis and shifting to oxidative phosphorylation, with loss of HK2/LDHA, PKM2-to-PKM1 splicing, and decreased c-MYC/N-MYC. Constitutive HK2/LDHA expression kills differentiating neurons, while increased PGC-1α/ERRγ maintain rather than increase metabolic and mitochondrial gene expression.
Key findings
- Differentiation from NPCs to neurons involves loss of HK2 and LDHA protein, a PKM splice switch from PKM2 to PKM1, and a neuron-specific OGDH splice form lacking a Ca²⁺-binding motif; c-MYC and N-MYC protein levels fall by ~70% and ~85%, respectively.
- Neurons show lower glycolytic/TCA metabolite levels and higher oxidative capacity: basal and maximum OCR rise from ~82 and 130 pmoles/min/10 µg in NPCs to ~98 and 183 in 3-week neurons, while lactate/glucose ratio falls from ~1.61 to ~0.35.
- Constitutive HK2 and LDHA expression during differentiation causes neuronal death: ~40% condensed nuclei versus ~6% in controls, with ~40% GFAP-positive glial cells versus ~4% in controls; extra pyruvate (5 mM) rescues neuronal death but not glial increase.
- PGC-1α and ERRγ increase ~3–4 fold and ~2.8–3.4 fold, respectively, and are required to maintain expression of glycolysis, TCA, and mitochondrial respiratory complex genes, even though most mitochondrial gene expression is unchanged versus NPCs; mtDNA copy number and protein mass both increase ~4-fold by 3 weeks.
Methods
- Human BJ iPSC-derived NPCs were differentiated for 1–3 weeks and validated by Sox2/Nestin and MAP2 staining; RNA-seq was performed on two NPC lines with duplicates, and data were mapped with STAR and quantified by FPKM.
- Metabolic profiling used GC-MS for glycolytic/TCA metabolites, Seahorse for OCR, lactate assays, immunoblotting/immunostaining, RT-PCR, ChIP for c-MYC/N-MYC binding, and lenti-shRNA knockdowns of HK2, LDHA, PGC-1α, or ERRγ.
- Direct neuronal conversion from fibroblasts was tested with PTB knockdown or Ngn2/Ascl1 overexpression; mouse neuroprogenitor differentiation and published mouse astrocyte/neuron RNA-seq were used for conservation checks.
Limitations
- The paper states that expression levels of metabolic enzymes do not completely reflect biochemical/physiological activities, and post-translational modifications were not explored.
- The paper notes that mitochondrial structure, dynamics, and matrix calcium were not investigated, and that protein degradation may also downregulate key metabolic enzymes.
- Evident from the text: the main differentiation model relies on human BJ iPSC-derived NPCs, with some key findings validated in mouse cells; 3-week cultures were used as developing neurons, and rare glial cells emerge later, so longer-term neuronal populations were not the primary focus.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 50 cited sources checked · 0 supported · 0 flagged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mitochondrial mass increases proportionally with neuronal mass growth”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a switch in pyruvate kinase gene splicing from PKM2 to PKM1”
- Also stated in: § Neuron-specific splicing of PKM and OGDH · plain
“NPCs mainly expressed PKM2, whereas neurons expressed PKM1”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Neuron-specific splicing of PKM and OGDH · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression”
- Also stated in: § HK2 and LDHA were off during neuronal differentiation · plain
“HK2 and LDHA mRNAs were about 15% and 25% of those in NPCs, but strikingly, both proteins almost completely disappeared upon differentiation”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § HK2 and LDHA were off during neuronal differentiation · plain
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“whose levels are unchanged compared to NPCs”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically.”
- Also stated in: § HK2 and LDHA were off during neuronal differentiation · plain
“Both c-MYC and N-MYC protein levels decreased significantly, by ~70% and ~85% respectively, once NPCs differentiated into neurons”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § HK2 and LDHA were off during neuronal differentiation · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After 3 weeks of differentiation, a majority (~85%) of cells expressed the neuronal marker MAP2”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Transcription profiling of neuronal differentiation from human NPCs
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the levels of citrate synthase (CS), isocitrate dehydrogenase (IDH2) and succinyl-CoA ligase β subunit (SUCLA2) were constant during differentiation”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > HK2 and LDHA were off during neuronal differentiation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The basal and maximum OCRs of NPCs were ~82 and 130 (pmoles/min/10 µg), whereas those in 3-week differentiated neurons were ~98 and 183, significantly higher than in NPCs”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Glycolytic and TCA metabolites and oxygen consumption rate in NPCs and neurons
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 43
- Probably not a substantial claim. 17
- The quote only partly states this claim. 1
In the paper
“OGDH, a key enzyme in the TCA cycle, has a novel and conserved neuronal splicing shift, resulting in the loss of a calcium binding motif.”
- Also stated in: § Neuron-specific splicing of PKM and OGDH · plain
“a stretch of 34 amino acids in OGDH1, containing a Ca2+-binding motif (Armstrong et al., 2014), is replaced by 45 amino acids specific to OGDHneu”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Introduction
What the sources say
- Not checked yetcites Armstrong et al., 2014
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Neuron-specific splicing of PKM and OGDH · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the levels of 3-phosphoglyerate (3PG) and pyruvate in neurons dropped to ~52% and 32% of those in NPCs”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Glycolytic and TCA metabolites and oxygen consumption rate in NPCs and neurons
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“citrate was ~32% of that in NPCs, α-ketoglutarate was ~17%, fumarate was ~30%, and malate was ~22%; succinate was relatively higher, at ~62%”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Glycolytic and TCA metabolites and oxygen consumption rate in NPCs and neurons
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HK2 and LDHA mRNAs were about 15% and 25% of those in NPCs, but strikingly, both proteins almost completely disappeared upon differentiation”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > HK2 and LDHA were off during neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“both HK2 and LDHA mRNA levels dropped, falling to ~8.5% and ~11% of the level in NPCs, respectively, and, consistently, their protein levels were also greatly decreased”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > HK2 and LDHA were off during neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“OGDHneu splicing is conserved in mouse neurons, whereas mouse astrocytes, like human astrocytes, only expressed OGDH1”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Neuron-specific splicing of PKM and OGDH
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“OGDH in NPCs (OGDH1) uses exon 4, whereas the isoform in neurons, here called OGDHneu, uses two adjacent exons”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Neuron-specific splicing of PKM and OGDH
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most of the down-regulated genes were cell cycle related, whereas up-regulated genes were enriched in neuronal function pathways”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Transcription profiling of neuronal differentiation from human NPCs
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the ratio was ~1.61 lactate/glucose for NPCs, while in neurons, it was ~0.35”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Glycolytic and TCA metabolites and oxygen consumption rate in NPCs and neurons
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TCA genes remained at the same level during differentiation; an exception was isocitrate dehydrogenase, IDH2, the mitochondrial isoform of IDH, which dropped nearly 50%”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Gene expression of glycolysis and TCA enzymes during neuronal differentiation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Except for PDK2, RNA levels of the other three PDKs declined significantly during neuronal differentiation; in contrast, PDP1 RNA levels increased ~2.5 fold at 3 weeks of differentiation”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Gene expression of glycolysis and TCA enzymes during neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both approaches generated Tuj1-positive neurons after 3 weeks of transduction.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > LDHA is down-regulated in neurons directly converted from fibroblasts
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“no significant difference was found between NPCs and neurons at 1 and 3 weeks, except for SDHB of complex II, which was consistently ~50% lower in neurons (Figure 5C).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, AMPK pT172 was clearly increased at day 4 of neuronal differentiation compared to control, but the phosphorylation returned to a level comparable to control at day 21, when extensive cell death had already occurred (Figure 4I).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Shutoff of aerobic glycolysis is critical for neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“after the first week, the neuronal mtDNA copy number doubled compared to NPCs, and at 3 weeks was increased to ~four fold.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The LDHA signal was clearly detected in GFAP-positive cells with anti-LDHA antibody (Figure 4E) or anti-FLAG antibody staining (Figure 4H), but there was no colocalization with MAP2, a neuronal marker.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Shutoff of aerobic glycolysis is critical for neuronal differentiation
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that PGC-1α was required to maintain the levels of ENO1 and PKM in glycolysis; CS, ACO2, OGDH and SUCLA2 in TCA cycle; TFAM and TFBM1 in mtDNA replication and transcription, and NRF1 (nuclear respiratory factor-1), a key transcription factor that activates nuclear genes encoding respiratory complex subunits (Figure 5F).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that during neuronal differentiation, UCP2 expression levels dropped significantly, and in 3-week neurons the UCP2 level was only 20% of that in NPCs (Figure 5—figure supplement 1)”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Surprisingly, even though neurons rely on oxidative phosphorylation to generate energy; the expression of TCA and mitochondrial genes is not increased.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Neurons rely on mitochondrial oxidative phosphorylation to meet energy demand.
In the paper
“deletion of lactate dehydrogenase A (LDHA) impairs maintenance and proliferation of hematopoietic stem and progenitor cells (Wang et al., 2014)”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Introduction
What the sources say
- Not checked yetcites Wang et al., 2014
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“PGC-1α knockout mice show obvious neurodegenerative pathology (Lin et al., 2004)”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Introduction
What the sources say
- Not checked yetcites Lin et al., 2004 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating an unknown mechanism linking mitochondrial biogenesis to cell size”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A pioneering study using embryonic Xenopus retina revealed that neural progenitor cells (NPCs) are less reliant on oxidative phosphorylation for ATP production than are non-dividing differentiated neurons, and the transition from glycolysis to oxidative phosphorylation is tightly coupled to neuronal differentiation”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Introduction
What the sources say
- Not checked yetcites Agathocleous et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Neurons rely on oxidative phosphorylation to meet energy demands.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Only high-quality NPC lines containing more than 90% Sox2 and Nestin double-positive cells were used for experiments.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Transcription profiling of neuronal differentiation from human NPCs
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The drastic decreases in HK2 and LDHA, the two key enzymes supporting aerobic glycolysis (DeBerardinis and Thompson, 2012; Dang, 2012), are consistent with neurons not having high flux aerobic glycolysis and exhibiting low lactate production.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > HK2 and LDHA were off during neuronal differentiation
What the sources say
- Not checked yetcites DeBerardinis and Thompson, 2012
- Not checked yetcites Dang, 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“MYC, a key transcription factor associated with cell cycle progression, directly activates HK2 and LDHA transcription, and the promoter regions of HK2 and LDHA contain MYC binding sites (5'-CACGTG-3'), also known as E box (Kim et al., 2004).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > HK2 and LDHA were off during neuronal differentiation
What the sources say
- Not checked yetcites Kim et al., 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Denton et al. (2016) also detected this splice form of OGDH in the whole brain tissue and pancreatic islets, calling it LS1, and, importantly, they confirmed that LS1 isoform is insensitive to Ca2+.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Neuron-specific splicing of PKM and OGDH
What the sources say
- Not checked yetcites Denton et al., 2016
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The median sequencing read yield for each sample was ~35 million 100-base reads, of which ~85% were mapped.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Transcription profiling of neuronal differentiation from human NPCs
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“overexpression of PGC-1α in cardiac cells triggers the upregulation of hundreds of genes in glycolysis, TCA and mitochondrial respiratory complexes (Rowe et al., 2010).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
What the sources say
- Not checked yetcites Rowe et al., 2010
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The results suggest that neurons cannot tolerate constitutive HK2 and LDHA expression and die during differentiation.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Shutoff of aerobic glycolysis is critical for neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It appears that although mitochondrial mass increases on a per cell basis, mitochondrial density remains largely unchanged during neuronal differentiation.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“A transcriptional circuit, including PGC-1 family coactivators, estrogen-related receptors (ERRs) and nuclear respiratory factor (NRF), is responsible for the transcription of metabolic and mitochondrial genes in multiple tissues, such as heart and skeletal muscle (Scarpulla et al., 2012).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
What the sources say
- Not checked yetcites Scarpulla et al., 2012 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“c-MYC and N-MYC redundantly promote neural progenitor cell proliferation in the developing brain, with the brains of double knockout mice exhibiting profoundly impaired growth (Wey and Knoepfler, 2010).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > HK2 and LDHA were off during neuronal differentiation
What the sources say
- Not checked yetcites Wey and Knoepfler, 2010
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Functional induced neurons (iN) can be generated directly from fibroblasts by forced expression of neural specific transcription factors, a process also called transdifferentiation (Vierbuchen et al., 2010).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > LDHA is down-regulated in neurons directly converted from fibroblasts
What the sources say
- Not checked yetcites Vierbuchen et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“PGC-1α is induced in the neonatal mouse heart concurrent with the increase of mitochondrial energy-producing capacity (Lehman et al., 2000).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
What the sources say
- Not checked yetcites Lehman et al., 2000 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“PGC-1α not only stimulates the induction of NRF1, but also binds to and coactivates the transcriptional function of NRF1 in muscle cells (Wu et al., 1999).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Result > Increased neuronal PGC-1α/ERRγ maintained the transcription of glycolysis, TCA and mitochondrial genes
What the sources say
- Not checked yetcites Wu et al., 1999
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“UCP2 is critical for maintaining stem cell glycolytic metabolism, and its level decreases during differentiation (Zhang et al., 2011; Yu et al., 2013).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
What the sources say
- Not checked yetcites Zhang et al., 2011
- Not checked yetcites Yu et al., 2013
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“MILS neurons also have very low expression of HK2 and LDHA, and do not exhibit a significant increase in mitochondrial density (Zheng et al., 2016).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
What the sources say
- Not checked yetcites Zheng et al., 2016
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The critical role of LDHA in aerobic glycolysis has been proven in cancer cells, and LDHA depletion greatly decreases aerobic glycolysis and increases mitochondrial OXPHOS activity (Fantin et al., 2006).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
What the sources say
- Not checked yetcites Fantin et al., 2006
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It appears that neurons cannot use aerobic glycolysis or mitochondrial biogenesis to compensate for energy shortage.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The A4 isozyme kinetically favors the conversion from pyruvate to lactate, while the B4 isozyme prefer converting lactate to pyruvate (Cahn et al., 1962).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
What the sources say
- Not checked yetcites Cahn et al., 1962
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In an iPSC-based disease model of maternally inherited Leign syndrome (MILS), an early childhood neurodegenerative disease due to ATP synthase defect, we found that MILS neurons but not their NPCs show severe energy deficiency; MILS NPCs generate more lactate than healthy control NPCs.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
What the sources say
- Not checked yetcites Zheng et al., 2016
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Glucose transporter levels dramatically decrease in neurons, which limits glucose uptake and the production of glycolytic pyruvate.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Shut-off of aerobic glycolysis is critical for neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fourth, the decrease in expression of PDKs and the increase in PDPs may result in more active pyruvate dehydrogenase complexes (PDC), as demonstrated by decreased phosphorylation at Ser 300 of PDH E1 alpha protein (PDHA1), promoting pyruvate entry into the TCA cycle.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“mitochondrial structure (cristae organization and size), dynamics (fusion and fission) and calcium concentration in the mitochondrial matrix are all involved in mitochondrial energy metabolism (Mishra and Chan, 2014).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
What the sources say
- Not checked yetcites Mishra and Chan, 2014
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, the decreased expression of HK2, and the GLUT1 and GLUT3 glucose transporters reduce glucose entry, terminating high flux glycolysis.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Molecular changes that define the neuronal energy preference for oxidative phosphorylation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For each time point, two experimental duplicates were used for each independent NPC line and its differentiated neurons.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Materials and methods > RNA sequencing
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“in a high-throughput screen to identify small molecules interfering with mitochondrial abundance, hundreds of compounds were found to be capable of changing the cellular mitochondrial content; the majority of them also change cell size accordingly (Kitami et al., 2012)”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Metabolic and mitochondrial gene transcription control in proliferating and post-mitotic differentiated cells
What the sources say
- Not checked yetcites Kitami et al., 2012
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This step is critical for the purity of NPCs; only colonies (type 4) showing sufficient maturity as described in Figure 1—figure supplement 2 were picked.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Materials and methods > Establishment of NPCs and neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“blocking neuronal oxidative utilization of lactate affects neuronal survival and even memory formation (Suzuki et al., 2011; Lee et al., 2012).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Shut-off of aerobic glycolysis is critical for neuronal differentiation
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“c-MYC activation in the myocardium of adult mice induces mitochondrial biogenesis and glycolysis but reduces PGC-1α level (Ahuja et al., 2010).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Metabolic and mitochondrial gene transcription control in proliferating and post-mitotic differentiated cells
What the sources say
- Not checked yetcites Ahuja et al., 2010
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“RNA-seq experiments were performed with two NPC lines established from independent iPSC clones.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Materials and methods > RNA sequencing
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“only samples with RIN greater than 8.5 were used for library preparation.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Materials and methods > RNA sequencing
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“E2F also upregulates mitochondrial genes, a function conserved from flies to mammals (Ambrus et al., 2013).”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Metabolic and mitochondrial gene transcription control in proliferating and post-mitotic differentiated cells
What the sources say
- Not checked yetcites Ambrus et al., 2013
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that glycolytic pyruvate deficiency is a major cause of death.”
§ Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation > Discussion > Shut-off of aerobic glycolysis is critical for neuronal differentiation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
The paper relies on this without support.
Little is known about the molecular basis of neurons' preference for oxidative phosphorylation or neuronal metabolic responses to energy crisis and their implications for disease progression.
“Little is known about the molecular basis of neurons’ preference for oxidative phosphorylation, or neuronal metabolic responses to the energy crisis and their implications for disease progression.”
The paper relies on this without support.
Neurons rely on oxidative phosphorylation to meet energy demands.
“Neurons rely on oxidative phosphorylation to meet energy demands.”
The paper relies on this without support.
Neurons rely on mitochondrial oxidative phosphorylation to meet energy demand.
“Neurons rely on mitochondrial oxidative phosphorylation to meet energy demand.”
The paper relies on this without support.
Aerobic glycolysis diverts pyruvate from mitochondrial oxidative phosphorylation for energy production by converting it into secreted lactate.
“As aerobic glycolysis diverts pyruvate from mitochondrial oxidative phosphorylation for energy production by converting it into secreted lactate”
The paper relies on this without support.
HK1 is still expressed in neurons.
“HK1 is still expressed in neurons”
The paper relies on this without support.
In proliferating NPCs, mitochondria are used for generation of biosynthetic precursors and mitochondria themselves have to be duplicated for daughter cells.
“mitochondria are used for generation of biosynthetic precursors in these proliferating cells, and mitochondria themselves have to be duplicated for daughter cells.”
The paper relies on this without support.
The expression levels of metabolic enzymes alone do not completely reflect their biochemical/physiological activities.
“the expression levels of metabolic enzymes alone do not completely reflect their biochemical/physiological activities”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In multiple tissue contexts, adult stem cells have been found to primarily engage in aerobic glycolysis.”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [205]
In the citing paper
“Upon lineage commitment and differentiation, however, cells increase their oxidation of pyruvate in the TCA cycle and display enhanced OXPHOS (203, 204, 205).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [205]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
NPC passage differs between the results and Figure 3 caption
MinorThe results say the HK2 and LDHA knockdown experiment used passage-3 NPCs, while the Figure 3C caption says passage 2.
“BJ NPC cells at passage 3 were infected with lenti-shRNAs targeting HK2 or LDHA.”
“NPCs at early passage (P2) were seeded in 24-well plates one day before infection.”
Figure 1 caption reverses the TCA and PDH panel assignments
MinorIn the caption's ordered list, panel H corresponds to TCA and panel I to PDH. The results instead cite panel I for TCA genes and panel H for PDH-complex genes.
“(G, H, I and J) Relative expression levels of the key metabolic genes in glycolysis, tricarboxylic acid cycle (TCA), pyruvate dehydrogenase (PDH) complex and pentose phosphate pathway.”
“Expression of the genes encoding the subunits of PDC itself, including PDHA1, PDHB, PDHX, DLAT, and DLD, showed no significant changes (Figure 1H).”
Citations
Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · cited 3×
“RNA-seq reactions were done on an Illumina HiSeq 2500 system (Illumina, San Diego, CA) and the sequenced reads were mapped to an annotated human genome (version GRch37/hg19) using STAR (Dobin et al., 2013).”
BackgroundMethodUnderstanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197 · cited 1×
“Most cancer cells use aerobic glycolysis to generate energy, a phenomenon called the Warburg effect, in which a large fraction of glycolytic pyruvate is converted into lactate (Vander Heiden et al., 2009).”
BackgroundTrapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390 · cited 3×
“…whether changes in alternative mRNA splicing occurred in glycolysis, TCA and mitochondrial respiratory complex genes during neuronal differentiation, the distributions of exonic RNA-seq reads were manually compared between NPCs and neurons using Integrative Genomics Viewer (Robinson et al., 2011).”
MethodInfluentialTrapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 12,145 · cited 1×
“The sequencing reads were mapped to a human reference genome by STAR and assembled with Cufflinks (Dobin et al., 2013; Trapnell et al., 2012).”
MethodMitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · cited 2×
“This result was consistent with a recent finding that mouse neurons exclusively expressed PKM1, whereas astrocytes only expressed PKM2 (Zhang et al., 2014).”
ResultWu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · cited 2×
“PGC-1a not only stimulates the induction of NRF1, but also binds to and coactivates the transcriptional function of NRF1 in muscle cells (Wu et al., 1999).”
BackgroundChronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R. S., Sherer, T., MacKenzie, G. M., Garcia‐Osuna, M., Panov, A. V., & Greenamyre, J. T. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,770 · cited 1×
“For example, chronic exposure of the brain to the lipophilic pesticide rotenone causes dopaminergic neuron degeneration (Betarbet et al., 2000).”
BackgroundHypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645 · cited 1×
“Moreover, under low oxygen condition, the transcription of glycolytic genes is upregu- lated by hypoxia-inducible factor (HIF), and increased glycolytic ATP produced by enhanced glyco- lytic flux can partially supply cellular energy demands (Iyer et al., 1998; Seagroves et al., 2001; Semenza, 2012).”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–500 of 666
Sowers, M. L., Anderson, A. P. P., Wrabl, J. O., & Yin, Y. W. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b04655 · Cited by 6
Park, D. I. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.04.017 · Cited by 9
Single-cell based elucidation of molecularly-distinct glioblastoma states and drug sensitivityPreprint
Ding, H., Burgenske, D. M., Zhao, W., Subramaniam, P. S., Bakken, K. K., He, L., Alvarez, M. J., Laise, P., Paull, E., Spinazzi, E. F., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/675439 · Cited by 8
“, and Hunter, T. (2016). Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation.”
BackgroundAutophagy–NAD+ axis: emerging insights into neuronal homeostasis and neurodegenerative diseases
Koçak, G., Dimas, M. M., Silva, L., Silva-Amaral, D., Sun, C., Cruddas, S., Barrett, T. G., Martins‐de‐Souza, D., Cunha‐Neto, E., Brocardo, P. S., et al. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1695486 · Cited by 8
“Neurons mainly generate ATP through oxidative phosphorylation (OXPHOS), in contrast to glial cells that rely mainly on glycolysis (Zheng et al., 2016).”
Henrich, A., & Scheiblich, H. (2026) · European Journal of Neuroscience · doi:10.1111/ejn.70463 · Cited by 8
“Because of these demands, neurons rely predominantly on oxidative phosphorylation (OXPHOS) rather than glycolysis (Koopman et al. 2013; Zheng et al. 2016).”
Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids
Menacho, C., Okawa, S., Álvarez‐Merz, I., Wittich, A., Muñoz‐Oreja, M., Lisowski, P., López-Martín, M., Pentimalli, T. M., Zakin, S., Thevandavakkam, M. A., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-71391-2 · Cited by 9
“This featureisusually interpreted as a consequenceof defective OXPHOS, which increases the reliance on glycolysis for ATP production, leading to a buildup of lactate 40 – 42 .”
InfluentialMorales, A. S. M., & Andrews, M. G. (2022) · Development · doi:10.1242/dev.200506 · Cited by 7
Neuronal glycolysis: focus on developmental morphogenesis and localized subcellular functions
Gallo, G. (2024) · Communicative & Integrative Biology · doi:10.1080/19420889.2024.2343532 · Cited by 7
“Consistently, neural progenitors and early developing neurons rely heavily on neuronal glycolysis for ATP generation and likely the related anabolic functions of glycolysis [10].”
BackgroundZhang, L., Xie, J., Zhang, Z., et al. (2022) · Current Microbiology · doi:10.1007/s00284-022-02844-2 · Cited by 7
“It is the coupling reaction of ADP and inorganic phosphoric acid to produce ATP through the energy released during the oxidation of substances in vivo [20].”
BackgroundSARS-CoV-2 leverages airway epithelial protective mechanism for viral infection
Greaney, A. M., Raredon, M. S. B., Kochugaeva, M. P., Niklason, L. E., & Levchenko, A. (2023) · iScience · doi:10.1016/j.isci.2023.106175 · Cited by 9
“This relationship may not be coincidental, since differentiation, even under homeostatic conditions, is frequently associated with increasing oxidative phosphorylation and oxidative stress (Drehmer et al., 2016; Shyh-Chang and Daley, 2015; Tatapudy et al., 2017; Zheng et al., 2016).”
Zhang, L., Wei, H., Yu, Y., Li, Q., Song, Z., Sun, Y., Li, P., Chen, J., Gan, J., Zhang, H., et al. (2023) · Aquaculture Reports · doi:10.1016/j.aqrep.2023.101672 · Cited by 8
High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts
Salti, A., Etemad, S., Cubero, M. S., Albertini, E., Kovacs-Szalka, B., Holzknecht, M., Cappuccio, E., Cavinato, M. S., Edenhofer, F., & Jansen‐Dürr, P. (2021) · Cells · doi:10.3390/cells10082040 · Cited by 7
“from PKM2 to its constitutively active isoform PKM1 and an upregulation of OXPHOSrelated genes has been observed [21,22].”
BackgroundPotential Mechanisms Driving Mitochondrial Motility Impairments in Developing Iron-Deficient Neurons
Bastian, T. W. (2019) · Journal of Experimental Neuroscience · doi:10.1177/1179069519858351 · Cited by 7
Metabolic Atlas of Early Human Cortex Identifies Regulators of Cell Fate TransitionsPreprint
Mil, J., Soto, J., Matulionis, N., Krall, A. S., Day, F., Stiles, L., Montales, K. P., Azizad, D. J., Gonzalez, C. E., Nano, P. R., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.10.642470 · Cited by 7
Next-generation direct reprogramming
Keshri, R., Detraux, D., Phal, A., McCurdy, C., Jhajharia, S., Chan, T. C., Mathieu, J., & Ruohola‐Baker, H. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1343106 · Cited by 7
“A metabolic remodeling is also observed in neuronal transdifferentiation (Zheng et al., 2016).”
BackgroundYin, Z., Kang, J.-H., Cheng, X., Gao, H., Huo, S., & Xu, H.-W. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01612 · Cited by 6
“Metabolic remodeling is important for cell reprogramming (Zheng et al., 2016; Cliff and Dalton, 2017).”
BackgroundCardiac Regeneration in Adult Zebrafish: A Review of Signaling and Metabolic Coordination
Mitra, A., Mandal, S., Banerjee, K., Ganguly, N., Sasmal, P., Banerjee, D., & Gupta, S. (2025) · Current Cardiology Reports · doi:10.1007/s11886-024-02162-y · Cited by 7
“Knocking down pkm2 reduces glycolytic activity in human umbilical vein endothelial cells [200] and intestinal stem cells [201], while increasing pkm1 levels [202, 203].”
Impairment of DET1 causes neurological defects and lethality in mice and humans
Karayel, Ö., Soung, A., Gurung, H. R., Schubert, A. F., Klaeger, S., Kschonsak, M., Al-Maraghi, A., Bhat, A. A., Akil, A. A., Dugger, D. L., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2422631122 · Cited by 8
“The transition from the predominantly glycolytic progenitor state to mitochondrial aerobic respiration in mature neurons is a crucial phase of neuronal differentiation ( 30 ).”
Varghese, N., Szabo, L., Cader, M. Z., Lejri, I., Grimm, A., & Eckert, A. (2025) · Communications Biology · doi:10.1038/s42003-025-08152-2 · Cited by 17
“Importantly,thesedifferenceswerealsoobservedintheiPSCsNs,asur-prisingoutcomenotpreviouslyreported 18,37 – 39 .”
Kumar, S., Jin, J., Park, H. Y., Kim, M. J., Chin, J., Lee, S., Kim, J., Kim, J., Choi, Y., & Park, K. (2022) · Endocrinology and Metabolism · doi:10.3803/enm.2022.1462 · Cited by 6
“Platelet-derived growth factor (PDGF)-stimulated VSMCs exhibit increases in basal respiration, maximal respiratory capacity, and adenosine triphosphate (ATP)-linked respiration in mitochondrial respiration analysis [10-12], whereas proliferation of VSMCs is suppressed when mitochondrial oxidative phosphorylation is in…”
BackgroundBaxi, A. B., Nemes, P., & Moody, S. A. (2023) · iScience · doi:10.1016/j.isci.2023.107665 · Cited by 6
“Experiments using human embryonic stem cells have demonstrated that dynamic regulation of glycolytic metabolism is critical for neural differentiation.(24,25) These experiments primarily indicate a modification of the glycolytic pathway such that pyruvate is shunted away frommitochondrial respiration in favor of lacta…”
BackgroundRecent Advances of MSCs in Renal IRI: From Injury to Renal Fibrosis
Niu, X., Xu, X., Xu, C., Cheuk, Y. C., & Rong, R. (2024) · Bioengineering · doi:10.3390/bioengineering11050432 · Cited by 7
“These modifications, in turn, control gene transcription and regulate cell differentiation [61–63].”
BackgroundAdaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration
Lane, A. R., Scher, N. E., Bhattacharjee, S., Zlatic, S. A., Roberts, A. M., Gokhale, A., Singleton, K. S., Duong, D. M., McKenna, M., Liu, W. L., et al. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-11-0512 · Cited by 6
Abou‐Shanab, A. M., Shouman, S., Hussein, A. E., Gaser, O. A., Magdy, S., Ashraf, E., Salah, R. A., Idris, O., & El‐Badri, N. (2025) · BMC Cancer · doi:10.1186/s12885-025-14442-z · Cited by 6
“The observed metabolic shift suggests enhanced mitochondrial respiration, corroborating established evidence that differentiated cells primarily utilize the OXPHOS pathway for energy production rather than glycolysis [107–109], due to a reduction in ATP demand [110].”
Teranishi, M., Kurose, T., Nakagawa, K., et al. (2023) · Regenerative Therapy · doi:10.1016/j.reth.2022.12.010 · Cited by 6
“PKM2 expression is shown to be highly elevated in neural progenitor cells during proliferative culture and declines, while PKM1 expression increases with neural differentiation [36].”
BackgroundHow does the neuronal proteostasis network react to cellular cues?
Nam, K. H., & Ordureau, A. (2024) · Biochemical Society Transactions · doi:10.1042/bst20230316 · Cited by 7
Methods to detect mitophagy in neurons during disease
Carter, F. E., Moore, M. E., & Pickrell, A. M. (2019) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2019.108351 · Cited by 8
Interpretable deep generative models for genomicsPreprint
Choi, Y., Li, R., & Quon, G. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.15.460498 · Cited by 6
Mitochondrial pyruvate metabolism regulates the activation of quiescent adult neural stem cellsPreprint
Petrelli, F., Scandella, V., Montessuit, S., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.31.494137 · Cited by 6
Hexokinase and Glycolysis: Between Brain Cells Life and Death
da Mata, L. R. S., Santos, L., & César, M. C. (2023) · Current Chemical Biology · doi:10.2174/2212796817666230510095530 · Cited by 7
Gupta, P. K., Barak, S., Feuermann, Y., Goobes, G., & Kaphzan, H. (2024) · Molecular Autism · doi:10.1186/s13229-024-00608-2 · Cited by 5
“It is possible that this further induces either a delay or an aberration in the metabolic switch between anaerobic glycolysis to oxidative phosphorylation that is required for the development of mature neurons, and possibly alters the developmental trajectory of embryonic brain cells [28–30].”
BackgroundSpinal motor neuron development and metabolism are transcriptionally regulated by nuclear factor IA
Gauberg, J., Moreno, K. B., Jayaraman, K., Abumeri, S., Jenkins, S., Salazar, A. M., Meharena, H. S., & Glasgow, S. M. (2025) · Science Advances · doi:10.1126/sciadv.adu3346 · Cited by 5
“Mitochondria change their morphology, size, numbers, and localization throughout development to match the energy demands on the cell ( 48 , 49 ).”
Fueling the Mind: Brain Metabolism in Health and Neurodevelopmental Disorders
Marano, D., Mariano, V., & Novarino, G. (2025) · Annual Review of Genetics · doi:10.1146/annurev-genet-111523-102424 · Cited by 6
Guardians of homeostasis: Natural products target metabolic reprogramming in Alzheimer’s disease
Zhang, Z., Xu, H., Zhao, F., Han, Z., Pan, J., Li, M., Guan, W., Jiang, P., Hao, Z., Zhang, Y., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.103005 · Cited by 5
Role of mitochondria in neuronal function and survival in the enteric and central nervous systems
KURAL, İ., Mombeek, L. M. M., & Wilson, D. M. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-06053-5 · Cited by 8
“…evidenced by (i) transcriptomic analyses during neurogenesis that reveal decreased expression of glycolytic genes, such as hexokinase 2 ( HK2) and L-Lactate Dehydrogenase A (LDHA) , and (ii) mitochondrial DNA (mtDNA) copy number measurements, which indicate an increase in mitochondrial mass [17].”
Huang, M., Liao, X., Wang, X., et al. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.83927 · Cited by 5
“Upon differentiation, ESCs oxidize most of glycolysis-derived pyruvate via OXPHOS, and the upregulated TCA cycle metabolites are resultant of OXPHOS in mitochondria [50].”
BackgroundNeuroglobin: A promising candidate to treat neurological diseases
Yañez, I. M., Torres-Cuevas, I., & Corral‐Debrinski, M. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01503 · Cited by 5
“During the differentiation of neural stem cells, energy metabolism encounters major changes; thus, a metabolic switch occurs from anaerobic glycolysis in NPCs to aerobic OXPHOS in differentiated neurons, which is critical for neuronal cell differentiation (Agostini et al., 2016; Zheng et al., 2016).”
Øhlenschlæger, M. S., Jensen, P., Havelund, J. F., Schmidt, S. I., Mohamed, F. A., Sutcliffe, M. A., Elmkvist, S. B., Criscuolo, L., Wingett, S., Chiaradia, I., et al. (2026) · Cell Reports Methods · doi:10.1016/j.crmeth.2025.101295 · Cited by 5
“Neuronal differentiation typically involves a metabolic shift from glycolysis to OXPHOS, accompanied by increased mitochondrial mass. 47,48 This process is regulated by transcription factors like PGC-1 α and TFAM, which also promote lysosomal biogenesis, 34,35,49 perhaps explaining the concomitant…”
Genome-wide translation control analysis of developing human neurons
Lins, É. M., Oliveira, N. C. M., Reis, O., Ferrasa, A., Herai, R. H., Muotri, A. R., Massirer, K. B., & Bengtson, M. H. (2022) · Molecular Brain · doi:10.1186/s13041-022-00940-9 · Cited by 4
Luo, H., Xu, J. L., Huang, D., Chen, Y.-Q., Liu, Y., Li, Y., & Chen, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1030390 · Cited by 9
“The major metabolic precursors for biosynthesis and energy generation come from the TCA cycle and glycolysis (Zheng et al., 2016).”
BackgroundGhani, M., Peleg, Z., Ujlaki, G., Tóth, M. E., Amsalu, H., Póliska, S., & Tar, K. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1342741 · Cited by 5
Sakuma, T., Mukai, Y., Yamaguchi, A., et al. (2024) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b23-00860 · Cited by 5
Pérez‐Cano, L., Boccuto, L., Sirci, F., Hidalgo, J. M., Valentini, S., Bosio, M., D’ardhuy, X. L., Skinner, C. D., Cascio, L., Srikanth, S., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12050991 · Cited by 6
“…neuronal progenitors and differentiated neurons will then require a metabolic reprogramming, from aerobic glycolysis to oxidative phosphorylation, that will allow the cells to switch from a fast production of small quantities of energy to a slower but more efficient production of ATP [34].”
BackgroundImmune Cell-NSPC interactions: Friend or foe in CNS injury and repair?
Zeng, C. (2025) · Differentiation · doi:10.1016/j.diff.2025.100855 · Cited by 5
Ren, S., Wang, W., Jia, M., et al. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/3855702 · Cited by 5
“0e insufficient catalysis of glucokinase causes the glucose transporter to reduce glucose entry, thereby interfering with the catalysis of key enzymes [37].”
BackgroundLee, H., Lee, H., Kim, H.-Y., Lee, H., Kim, H., & Choi, H. (2019) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-019-01922-y · Cited by 5
Cao, Y. (2020) · Preprints.org · doi:10.20944/preprints202012.0122.v1 · Cited by 5
Gao, X., Di, X., Li, J., Kang, Y., Xie, W., Sun, L., & Zhang, J. (2023) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-023-01449-4 · Cited by 4
“Many types of cells, including stem cells [5], neurons [6], immune cells [7] and osteoclasts [8], have reported * Lijun Sun sunlijun@snnu.”
BackgroundMitochondrial Microproteins: Emerging Regulators in Neurodevelopment and Neurodegeneration
Borghol, N., Yandiev, S., & Courchet, J. (2025) · BioEssays · doi:10.1002/bies.70058 · Cited by 3
“Although it has not been demonstrated, it is likely that MP31 influences neural differentiation and maturation since the regulation of both glycolytic and mitochondrial metabolism affects the cell fate of NPC and developing neurons [86, 87].”
Danačíková, Š., Pecina, P., Pecinová, A., Svoboda, J., Vondrášek, D., Basello, D. A., Čajka, T., Hadraba, D., Mráček, T., Kořínek, V., et al. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05284-8 · Cited by 4
“In line with in vivo evidence [2, 3, 81], we observed coordinated shift from glycolysis toward OXPHOS, increased mitochondrial content, and enhanced redox capacity.”
InfluentialRomero-Morales, A. I., & Gama, V. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.840265 · Cited by 5
MitoRUSH as a tool to study the efficiency of mitochondrial import in complex I-deficient cells
Wasilewski, M., Mohanraj, K., Zakrzewski, M., Serwa, R. A., & Chacińska, A. (2025) · Journal of Cell Science · doi:10.1242/jcs.263701 · Cited by 4
Bordi, M., Testa, B., Compagnucci, C., Colasuonno, F., Cipressa, F., Betterini, E., Mancini, A., Carsetti, C., Salvatori, I., Ferraina, C., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116230 · Cited by 4
Mitochondrial remodelling—a vicious cycle in diabetic complications
Sherkhane, B., Gundu, C., Sood, A., Khatri, D. K., & Singh, S. B. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06408-8 · Cited by 5
“Neurons being highly differentiated cells look upon mitochondria to meet constant energy requirements for survival and synaptic integrity [59].”
BackgroundDirect Reprogramming in Bone and Joint Degenerative Diseases: Applications, Obstacles and Directions
Shi, K., Li, F., Tao, Y., & Chen, Q. (2022) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x17666220810142943 · Cited by 3
Genetic modifiers of synucleinopathies—lessons from experimental models
Lee, R. M. Q., & Koh, T. (2023) · Oxford Open Neuroscience · doi:10.1093/oons/kvad001 · Cited by 4
“…modeling synucleinopathy in cultured cells or organoids, it is unclear what in vitro correlate of biological aging should be [302]; in cases where proliferating cells are used to model post-mitotic neurons, it is possible that differences in cellular physiology may be a confounding factor [303].”
BackgroundKałuzińska‐Kołat, Ż., Kołat, D., Kośla, K., Płuciennik, E., & Bednarek, A. K. (2023) · World Journal of Stem Cells · doi:10.4252/wjsc.v15.i5.302 · Cited by 4
Hofstra, B., Hoeksema, E. E., Kas, M. J., & Verbeek, D. S. (2024) · Neurobiology of Stress · doi:10.1016/j.ynstr.2024.100643 · Cited by 7
“During this period, progenitor cells transition from glycolysis to oxidative phosphorylation as they transition to neurons, increasing the demand for oxidative phosphorylation (Zheng et al., 2016).”
Exploiting metabolic vulnerability in glioblastoma using a brain-penetrant drug with a safe profile
Burban, A., Tessier, C., Larroquette, M., Guyon, J., Lubiato, C., Pinglaut, M., Toujas, M., Galvis, J., Dartigues, B., Georget, E., et al. (2025) · EMBO Molecular Medicine · doi:10.1038/s44321-025-00195-6 · Cited by 7
“This could be explained by the fact that hNPCs have distinct metabolic pro fi le compared to BTSCs, where they rely on glycolysis rather than OXPHOS (Beckervordersandforth et al, 2017; Khacho et al, 2016; Zheng et al, 2016).”
Diet and Cancer Metabolic Reprogramming
Bhattacharya, S. (2021) · Cancer Reports and Reviews · doi:10.15761/crr.1000233 · Cited by 4
Triebelhorn, J., Cardon, I., Kuffner, K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.30.441774 · Cited by 4
Lisowski, P., Lickfett, S., Rybak‐Wolf, A., Le, S., Dykstra, W., Mlody, B., Menacho, C., Roth, P., Richter, Y., Kulka, L. A. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.03.543551 · Cited by 4
RB1 controls differentiation through positive regulation of phosphoglycerate mutases
Kohno, S., Okahashi, N., Wan, Y., Yu, H., Takegami, Y., Linn, P., Nagatani, N., Kitajima, S., Kawada, T., Matsuda, F., et al. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07850-3 · Cited by 4
Sidibe, D. K., Smith, E. M., Spivey, M. L., Vogel, M. C., & Maday, S. (2026) · PLoS ONE · doi:10.1371/journal.pone.0345890 · Cited by 4
Gu, W., Wang, X., Solmonson, A., Cai, L., Xiao, Y., Tasdogan, A., Franklin, J., Zhang, Y., Zhang, H., Westfall, A. K., et al. (2026) · Journal of Clinical Investigation · doi:10.1172/jci197010 · Cited by 3
“We also evaluated MYCN given its overlap with MYC in neural progenitors (34).”
Zelentsova, A. S., Borisova, A. Y., Shmigerova, V. S., Skorkina, M. Y., & Deykin, A. V. (2024) · Genes and Cells · doi:10.17816/gc529662 · Cited by 3
Vancamp, P., Frapin, M., Parnet, P., & Amarger, V. (2024) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2024.100339 · Cited by 5
“To meet the increased energy demands, a neural progenitor cell undergoes mitochondrial biogenesis and a metabolic shift from glycolysis to oxidative phosphorylation to upscale ATP triphosphate) production (106,107).”
BackgroundRemodeling of Mitochondria–Endoplasmic Reticulum Contact Sites Accompanies LUHMES Differentiation
Esfahani, E. N., Knedlík, T., Shin, S. H., Rebelo, A. P. M., Mario, A. D., Vianello, C., Persano, L., Rampazzo, E., Edomi, P., Bean, C., et al. (2025) · Biomolecules · doi:10.3390/biom15010126 · Cited by 4
“As MERCs are a fundamental platform to shape cell metabolism [37], these changes might be necessary to sustain the metabolic reprogramming that accompanies the transition from NPCs to neurons [6,9].”
Slater, P. G., Domínguez-Romero, M. E., Campos, G., Aravena, V., Cavieres-Lepe, J., & Eisner, V. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1529093 · Cited by 4
“In contrast, a cell that inherits older mitochondria and shifts its metabolism toward oxidative phosphorylation is the one that differentiates (Yanes et al., 2010; Zheng et al., 2016).”
Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination
Gu, J., Yang, M., Zhang, L., Liu, Y., Yan, R., Pan, D., Qian, X., Hu, H., Chu, D., Hu, C., et al. (2025) · The Journal of Cell Biology · doi:10.1083/jcb.202405142 · Cited by 3
Meng, C., Yang, L., Huang, Y., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094014 · Cited by 3
“…closely associated with energy metabolism (Figure 7), this study verified the effect of Ni 2+ on cellular energy metabolism via ATP content assays [36,37]. after 48 h of treatment with 100, 200, or 500 µM The changes in the ATP content of neurons after 48 h of treatment with 100, 200, or 500 µ M…”
The TBXT rs2305089 SNP links the benign notochordal cell tumour and chordoma
Usher, I., O’Donnell, P., Ligammari, L., Harder, D., Brown, W., Choi, D., Cool, P., Cottone, L., & Flanagan, A. M. (2025) · The Journal of Pathology · doi:10.1002/path.6427 · Cited by 3
Luo, X., Assal, D. C. E., Liu, Y., Ranjbar, S., & Fleming, R. M. T. (2025) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2025.1594330 · Cited by 3
Koetsier, J., Eijssen, L., Schurgers, L. J., Curfs, L., Reutelingsperger, C. P. M., & Sangani, N. B. (2025) · Communications Biology · doi:10.1038/s42003-025-08330-2 · Cited by 3
“Moreover, mitochondrial function, in particular the shift to oxidative phosphorylation, is required for the induction of neuronal differentiation 25 .”
Hwang, D., Kim, T., Kyun, S., Jang, I., Park, H., Kim, S.-W., Han, J.-S., So, J.-M., Lee, C.-H., Park, J.-H., et al. (2025) · Physical Activity and Nutrition · doi:10.20463/pan.2025.0011 · Cited by 4
Post-transcriptional regulation of mitochondrial function
Schatton, D., & Rugarli, E. I. (2017) · Current Opinion in Physiology · doi:10.1016/j.cophys.2017.12.008 · Cited by 3
Dierolf, J. G., Hunter, H., Watson, A. J., & Betts, D. H. (2022) · Stem Cells and Development · doi:10.1089/scd.2021.0347 · Cited by 3
Shih, L.-K., Mukherjee, S., & Brat, D. J. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03009-9 · Cited by 3
“Glycolysis is critical for several homeostatic metabolic processes and adaptations, yet in the context of NSCs, it is also known to promote self-renewing division, with oxidative phosphorylation favoring cellular differentiation [56].”
BackgroundShi, L., Li, H., Wang, Z., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175474 · Cited by 3
Temporal transcriptional control of neural induction in human induced pluripotent stem cells
Gupta, S., Polit, L. D., Fitzgerald, M., Rowland, H. A., Murali, D., Buckley, N. J., & Subramaniam, S. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1139287 · Cited by 3
“…source of energy required to maintain stem cell functions, early differentiation of human pluripotent stem cells (hiPSC) has been reported to be accompanied by a switch from glycolysis to oxidative phosphorylation (Zhang et al., 2012; Zheng et al., 2016) owing to the increased energy demands.”
BackgroundMurata, Y., Jo, J., & Tabata, Y. (2023) · ACS Sensors · doi:10.1021/acssensors.3c00106 · Cited by 3
Tan, S., Yu, H., Xu, Y., Zhao, Y., & Lou, G. (2023) · Medical Oncology · doi:10.1007/s12032-023-02144-0 · Cited by 4
Kolotyeva, N. A., Gilmiyarova, F. N., Сергеевич, А. А., Baranich, T. I., Rozanova, N. A., Kukla, M. V., Tregub, P. P., & Salmina, A. B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914709 · Cited by 3
“Along with proliferation and differentiation, immature neuronal cells gradually reduce glycolysis and fatty acid oxidation but activate mitochondrial oxidative phosphorylation [95–99].”
BackgroundAgarwala, S., Dhabal, S., & Mitra, K. (2024) · Open Biology · doi:10.1098/rsob.230279 · Cited by 3
“On the other hand, the cell differentiation process is associated with a dramatic increase in mitochondrial content [2,7,46,72,83,85].”
BackgroundMatrella, M. L., Valletti, A., Gigante, I., Rasmo, D. D., Signorile, A., Russo, S., Lobasso, S., Lobraico, D., Dibattista, M., Pacelli, C., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-57613-x · Cited by 5
Transcriptome Analysis of Myocardial Ischemic-Hypoxic Injury in Rats and Hypoxic H9C2 Cells
Niu, N., Miao, H., & Ren, H. (2024) · ESC Heart Failure · doi:10.1002/ehf2.14903 · Cited by 2
Visualizing metabolic regulation using metabolic biosensors during sea urchin embryogenesis
Furze, A. R., Waldron, A. L., & Yajima, M. (2024) · Developmental Biology · doi:10.1016/j.ydbio.2024.08.003 · Cited by 4
GSK3 coordinately regulates mitochondrial activity and nucleotide metabolism in quiescent oocytes
Eller, L. R., Wang, L., Gok, M. O., Hocaoglu, H., Qin, S., Gupta, P., & Sieber, M. (2025) · Biology Open · doi:10.1242/bio.061815 · Cited by 3
Heterogeneity of GRIM-19 Expression in the Adult Mouse Brain
Hwang, S.-N., Kim, J.-C., & Kim, S.-Y. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-019-00689-1 · Cited by 3
Nakamura, A., Okamoto, M., Maeda, A., Jiang, H., Sugawara, K., Kitatani, K., Takekoshi, S., Fujisawa, A., Yamamoto, Y., & Kashiba, M. (2022) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.21-107 · Cited by 3
Cross-Organ Transcriptomic Comparison Reveals Universal Factors During Maturation
Kambhampati, S., Murphy, S. A., Uosaki, H., & Kwon, C. (2022) · Journal of Computational Biology · doi:10.1089/cmb.2021.0349 · Cited by 3
Energy Metabolism | 2-Oxoglutarate Dehydrogenase Complex
Bunik, V. I., Wagner, T., & Bellinzoni, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819460-7.00127-4 · Cited by 3
Preservation of an Aging-Associated Mitochondrial Signature in Advanced Human Neuronal ModelsPreprint
Varghese, N., Szabo, L., Cader, M. Z., Lejri, I., Grimm, A., & Eckert, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.28.587193 · Cited by 3
NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency
Cendrowski, J., Wróbel, M., Mazur, M., Jary, B., Maurya, R., Wang, S., Korostyński, M., Dziewulska, A., Rohm, M., Kuropka, P., et al. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05490-y · Cited by 2
Photobiomodulation therapy increases neural stem cell pool in aged 3xTg-AD mice
Johnson, K. J., Johnson, K. M., Grant, A. C., Taglialatela, G., & Micci, M. (2025) · PLoS ONE · doi:10.1371/journal.pone.0321668 · Cited by 2
“PBM is known to increase mitochondrial metabolism and modulate redox homestasis [49,60,61], both of which also contribute to proliferation and survival of NSC and maturation of adult-born neurons [62–64].”
Masin, L., Zhang, A., Bergmans, S., & Moons, L. (2025) · BioEssays · doi:10.1002/bies.70037 · Cited by 2
“Differentiation of neuronal progenitor cells into neurons is accompanied by a shift from glycolysis to oxidative phosphorylation[65–67].”
Hedgehog signaling activation rescues hypoxia-induced ferroptosis in human brain organoids
Yi, S., Huang, M., Xian, C., Kong, X., Yin, S., Peng, J., Li, H., Jiang, Y. Q., Xie, B., & Xie, H. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00338 · Cited by 4
Disanza, B., Porcari, G. S., Finoti, L. S., Ramos-Rodriguez, L., Burris, D. M., McDonough, J. A., Ning, G., Fagan, G., Helman, G., Weiss, E., et al. (2025) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2025.100525 · Cited by 2
“58 Therefore, it is possible that excess BCAAs in BCAT1-deficient neurons are shunted into the mitochondria for oxidation, preventing accumulation.”
Folic Acid Metabolism and Its Impact on Neurogenesis: Molecular Mechanisms and Therapeutic Potential
Li, W., Tian, Y., & Ma, S. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05717-y · Cited by 3
“Second, increasing evidence suggests that NSCs need to transition their energy metabolism from glycolysis to oxidative phosphorylation to meet demands as they shift from quiescence to activity [167, 168].”
Huang, C., Babu, V. S., Bammidi, S., Arnold, J., Ebeling, M., Widmer, G., Strassburger, P., Lazendic, M., Grüner, S., Koester, J., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08491-w · Cited by 2
“7h).”
Metadata
- Authors
- Zheng, X., Boyer, L., Jin, M., Mertens, J., Kim, Y., Ma, L., Ma, L., Hamm, M., Gage, F. H., & Hunter, T.
- Affiliations
- Salk Institute for Biological Studies (US)
- Laboratory of Genetics, Salk Institute, La Jolla, United States
- Corresponding author
- Gage, Fred H
- Hunter, Tony
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-06-10
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4963198
- OpenAlex
- W2416068580
- Semantic Scholar
- fbed50febe18cd07bb8e0c7a00e748286b5070dc
- Cited by
- 671
- References
- 77
- Citations by year
- 2026: 82 · 2025: 76 · 2024: 84 · 2023: 81 · 2022: 74 · 2021: 85 · 2020: 65 · 2019: 49 · 2018: 39 · 2017: 33 · 2016: 1
- FWCI
- 20.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- California Institute for Regenerative Medicine (TR2-01778)
- Salk Pioneer postdoctoral fellowship
- The G. Harold and Leila Y. Mathers Foundation
- JPB Foundation
- Leona M. and Harry B. Helmsley Charitable Trust (#2012-PG-MED002)
- National Institutes of Health (CA14195, CA80100, CA82683)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metabolic reprogramming, neuronal differentiation, aerobic glycolysis, oxidative phosphorylation, hexokinase 2, LDHA, c-Myc, MYCN, PGC-1α, estrogen-related receptor gamma, mitochondrial biogenesis, neural progenitor cells, neuronal cell death, mitochondrial mass
- MeSH terms
- Aerobiosis, Cell Differentiation, Cells, Cultured, Glycolysis, Humans, Metabolism, Oxidative Phosphorylation, Gene Expression Regulation, Developmental, Neural Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
