Shared and distinct microRNA profiles between HT22, N2A and SH-SY5Y cell lines and primary mouse hippocampal neurons
Open accessAbstract
MicroRNAs (miRNA) are small non-coding RNAs that are key negative regulators of gene expression. Their roles include shaping the gene expression landscape during and after brain development by defining and maintaining levels of proteins that generate the distinct morphological and functional properties of neurons and other brain cell types. HT22, N2A, and SH-SY5Y are common immortalized neuronal cell lines that offer simple, less expensive, and time-saving options for in vitro modelling to evaluate miRNA functions. The extent to which these lines reflect primary neurons remains, however, unclear. Here, we benchmarked the miRNA profiles of cultured mouse hippocampal neurons against Argonaute-loaded miRNAs in the adult mouse hippocampus and miRNA data from the hippocampus of control human donors. We then compared the miRNA expression landscape in HT22, N2A and SH-SY5Y against mouse hippocampal primary cell cultures. We profiled over 700 miRNAs across the lines and detected 310 miRNAs in all four cell types. This included detection of neuron-enriched miRNAs such as miR-124 and miR-128, although the cell lines typically displayed lower levels of these than in primary neurons and reference adult hippocampal tissue. The miRNA profile in the HT22 cell line showed the highest correlation to the mouse primary neuronal cultures. Together, this study provides a dataset on basal miRNA expression across commonly used cell lines for neuroscience research and evidence for both conserved and distinct profiles that should be used to inform decisions on cell lines for modelling brain and miRNA research.
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Written from the paper’s full text.
TL;DR
This study benchmarks basal microRNA profiles of HT22, N2A, and SH-SY5Y cell lines against primary mouse hippocampal neurons and adult mouse/human hippocampal miRNA data. It finds substantial overlap but generally lower levels of neuron-enriched miRNAs in cell lines, with HT22 showing the highest correlation to primary mouse hippocampal neurons.
Key findings
- Primary mouse hippocampal neurons (DIV10) shared 78% of expressed miRNAs with Ago2-bound miRNAs from adult mouse hippocampus and 91% with human hippocampus; 119 miRNAs were common across all three, with only 8 exclusively detected in primary hippocampal neurons.
- Across primary neurons and the three cell lines, 310 miRNAs were detected; 98 (32%) were common to all four cell types. Unique counts were 13 miRNAs in primary neurons, 7 in HT22, 20 in N2A, and 61 in SH-SY5Y.
- HT22 had the highest correlation with primary mouse hippocampal neurons (r = 0.735, MSE = 8.515), N2A the lowest (r = 0.564, MSE = 13.444), and SH-SY5Y intermediate (r = 0.715, MSE = 8.443). HT22 also had the highest proportion of similarly expressed miRNAs (57%), followed by SH-SY5Y (43%) and N2A (38%).
- Neuron-enriched miRNAs such as miR-124, miR-128, miR-132, miR-212, and miR-218 were detected but generally lower in cell lines; some were absent (miR-129 not detected in HT22 or N2A, miR-134 not in HT22, miR-135a not in N2A). N2A versus SH-SY5Y detected 200 miRNAs, with 59 lower and 50 higher in N2A.
Methods
- Primary hippocampal neurons were prepared from embryonic day 18 C57Bl/6J mice and cultured to day in vitro 10; HT22, N2A, and SH-SY5Y cells were cultured and harvested 48 hours after plating, with triplicate independent cultures after four passages.
- miRNA profiling used the TaqMan OpenArray rodent microRNA panel (750 mouse/rat miRNAs) and qPCR, with 100 ng RNA input. Analysis in R included filtering (AmpScore ≥ 1.24, Cqconf ≥ 0.8, Ct > 10 and < 35), inclusion if present in at least 2 of 3 samples per group, mean Ct imputation, quantile normalization with qpcrNorm, PCA, Pearson correlation and MSE, limma differential expression (FDR < 0.05), ΔΔCt, ANOVA with Dunnett test, and 1000 bootstrapping iterations.
- Human control hippocampal RNA-seq from previously available data was analyzed with edgeR (count > 10, ~8 million reads, miRNAs present in all 3 samples), log CPM transformed to the Ct range, then merged and quantile normalized with the qPCR data.
Limitations
- The paper states that the OpenArray platform has a pre-selected number of miRNAs, so the full repertoire was not captured and isomiRs and editing were missed; human primary neurons (e.g., iPSC-derived) were not included; only basal miRNA expression was assessed, so responses to stressors cannot be inferred; and cell lines were compared to mature hippocampal neurons, not neural progenitors, leaving maturation-state differences unresolved.
- The authors also note that the cell lines were not differentiated. Evident from the methods, human SH-SY5Y cells were profiled on a rodent miRNA panel, which may underrepresent human-specific miRNAs; the paper notes human-specific brain miRNAs exist but does not list this as a limitation.
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1 of 25 cited sources checked · 1 supported · 0 flagged
- Findingown data
miRNAs such as miR-16, miR-30c, miR-125a have similar expression levels in the four cell types.
“miRNAs such as miR-16, miR-30c, miR-125a have similar expression levels in the four cell types (Fig 2D).”
Quote in the paperNot a substantial claim - Findingown data
7 miRNAs were detected only in HT22.
“13 miRNAs were detected only in the primary hippocampal neurons, 7 in HT22, 20 in N2A, and 61 in SH-SY5Y (Fig 2C).”
Quote in the paperNot a substantial claim - Findingown data
Neuron-enriched miRNAs such as miR-124 and miR-128 were detected in the cell lines.
“This included detection of neuron-enriched miRNAs such as miR-124 and miR-128”
Quote in the paperNot a substantial claim - Findingown data
13 miRNAs were detected only in primary hippocampal neurons.
“13 miRNAs were detected only in the primary hippocampal neurons, 7 in HT22, 20 in N2A, and 61 in SH-SY5Y (Fig 2C).”
Quote in the paperNot a substantial claim - Findingown data
PCA using total miRNA datasets showed separation of primary hippocampal neurons, HT22, N2A, and SH-SY5Y into four distinctive groups.
“Principal Component Analysis (PCA) using the total miRNA datasets from each cell type showed separation of primary hippocampal neurons, HT22, N2A, and SH-SY5Y into four distinctive groups (Fig 2B).”
Quote in the paperSubstantial claim
- Findingown data
Primary hippocampal neurons showed the highest expression of known neuron-enriched miRNAs compared to immortalized cell lines, including miR-128, miR-132, miR-212 and miR-218.
“Primary hippocampal neurons showed the highest expression of known neuron-enriched miRNAs compared to the immortalized cell lines, including miR-128, miR-132, miR-212 and miR-218 (Fig 3B).”
Quote in the paperSubstantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingown data
The miRNA profile in the HT22 cell line showed the highest correlation to the mouse primary neuronal cultures.
“The miRNA profile in the HT22 cell line showed the highest correlation to the mouse primary neuronal cultures.”
- Also stated in: § High correlation between miRNA profile in HT22 cells and primary mouse hippocampal neurons · plain
“This determined that HT22 cells had the highest correlation level (r = 0.735, MSE = 8.515. Fig 4A)”
Quote in the paperSubstantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Also stated in: § High correlation between miRNA profile in HT22 cells and primary mouse hippocampal neurons · plain
- Findingcitation
Of 160 detected miRNAs in primary neurons, 158 were identified as highly enriched in neurons, including miR-128, miR-132, miR-134 and miR-218.
“Then, we focused on the cell expression of the 160 detected miRNAs in primary neurons, 158 miRNAs were identified as highly enriched in neurons, including miR-128, miR-132, miR-134 and miR-218 [9] (Fig 1D, top panel).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] TJ Nowakowski, 2013, MicroRNA-92b regulates the development of intermediate cortical progenitors in embryonic mouse brain, Proc Natl Acad Sci U S A source
Not checked in the free run.
- Findingown data
miR-9, miR-132, miR-138 and miR-218 were highly expressed in neurons compared to immortalized cell lines.
“In contrast, miR-9, miR-132, miR-138 and miR-218 were highly expressed in neurons compared to the immortalized cell lines (Figs 2D and S2).”
Quote in the paperSubstantial claim - Findingown data
The resampled distribution from 1000 bootstrapping iterations was significantly different from the distribution in the observed miRNA profile.
“This revealed that the resampled distribution was significantly different from the distribution in our profile (S1 Fig)”
Quote in the paperSubstantial claim - Findingown data
Of the 310 miRNAs detected across the four cell types, 98 (32%) were commonly detected in all cell types.
“Of these, 32% (98 miRNAs) were commonly detected in all the cell types.”
Quote in the paperSubstantial claim - Findingown data
In profiling over 700 miRNAs, 310 miRNAs were detected across the four cell types (primary mouse hippocampal neurons, HT22, N2A, SH-SY5Y).
“We profiled over 700 miRNAs across the lines and detected 310 miRNAs in all four cell types.”
- Also stated in: § miRNA profiles in primary hippocampal neurons and HT22, N2A, and SH-SY5Y cell lines · plain
“We detected 310 miRNAs in the four cell types (Fig 2C).”
Quote in the paperSubstantial claim - Also stated in: § miRNA profiles in primary hippocampal neurons and HT22, N2A, and SH-SY5Y cell lines · plain
- Findingown data
119 miRNAs were commonly detected among primary mouse hippocampal neurons, adult mouse hippocampus Ago2-bound miRNAs, and adult human hippocampus.
“When we compared all three groups, 119 miRNAs were commonly detected, including various neuronal expressed miRNAs (Fig 1C) such as miR-128-, miR-132, miR-134, miR-135a, miR-181a/c, miR-212 and miR-218.”
Quote in the paperSubstantial claim - Findingcitation
Primary neurons displayed high expression of miRNAs linked to neurological disorders such as epilepsy, including miR-129a, miR-134, miR-135a and miR-146a.
“The primary neurons also displayed high expression of miRNAs linked to neurological disorders such as epilepsy, including miR-129a, miR-134, miR-135a and miR-146a [30].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] GP Brennan, 2020, MicroRNAs as regulators of brain function and targets for treatment of epilepsy, Nat Rev Neurol source
- Findingown data
SH-SY5Y and N2A cell lines displayed the highest overlap with primary neurons, with 10 and 9 miRNAs respectively.
“The SH-SY5Y and N2A cell lines displayed the highest overlap with primary neurons, with 10 and 9 miRNAs respectively.”
Quote in the paperSubstantial claim - Findingown data
A higher proportion of non-neuronal miRNA was detected in hippocampal tissue from mice and human brain tissue, 3% in both data sets.
“A higher proportion of non-neuronal miRNA was detected in hippocampal tissue from mice (Fig 1D, middle panel) and human brain tissue (Fig 1D, bottom panel); 3% in both data sets.”
Quote in the paperNot a substantial claim - Findingown data
61 miRNAs were detected only in SH-SY5Y.
“13 miRNAs were detected only in the primary hippocampal neurons, 7 in HT22, 20 in N2A, and 61 in SH-SY5Y (Fig 2C).”
Quote in the paperNot a substantial claim - Findingown data
78% of expressed miRNAs in primary mouse hippocampal neurons (DIV10) were also among those actively loaded in the RISC in the adult mouse hippocampus.
“When compared with mouse tissue, we found that 78% of the expressed miRNAs in our primary mouse neurons were also among those actively loaded in the RISC in the mouse brain (Fig 1A).”
Quote in the paperSubstantial claim - Findingown data
20 miRNAs were detected only in N2A.
“13 miRNAs were detected only in the primary hippocampal neurons, 7 in HT22, 20 in N2A, and 61 in SH-SY5Y (Fig 2C).”
Quote in the paperNot a substantial claim - Findingown data
The cell lines typically displayed lower levels of neuron-enriched miRNAs such as miR-124 and miR-128 than primary neurons and reference adult hippocampal tissue.
“although the cell lines typically displayed lower levels of these than in primary neurons and reference adult hippocampal tissue.”
Quote in the paperSubstantial claim - Findingown data
Only 8 miRNAs were exclusively detected in primary hippocampal neurons (miR-44b, miR-422a, miR-551b, miR-601, miR-659, miR-661, miR-672, miR-1244).
“Of note, only 8 miRNAs were exclusively detected in primary hippocampal neurons (Fig 1C; miR-44b, miR-422a, miR-551b, miR-601, miR-659, miR-661, miR-672 and miR-1244).”
Quote in the paperNot a substantial claim - Findingcitation
Primary neurons displayed low levels of miRNAs involved in cell proliferation, including the miR-17/92 cluster (miR-27, miR-18 and miR-92).
“In contrast, primary neurons displayed low levels of miRNAs involved in cell proliferation, including the miR-17/92 cluster (miR-27, miR-18 and miR-92) [47] (Fig 2B).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] E Mogilyansky, 2013, The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease, Cell Death Differ source
- Findingown data
HT22 and primary hippocampal neurons had only 1 miRNA exclusively detected in both cell types.
“HT22 and the primary hippocampal neuron had only 1 miRNA exclusively detected in both cell types (Fig 2C).”
Quote in the paperNot a substantial claim - Findingown data
91% of expressed miRNAs in primary mouse hippocampal neurons were also detected in adult human hippocampus.
“When compared with human hippocampus, 91% of the expressed miRNAs in our primary mouse neurons were also detected in the brain tissue (Fig 1B).”
Quote in the paperSubstantial claim - Findingown data
Axon guidance and developmental biology was the pathway found between primary hippocampal neurons and N2A cells.
“Axon guidance and developmental biology was found between primary hippocampal neurons and N2A.”
Quote in the paperNot a substantial claim - Findingown data
N2A had the lowest correlation level with primary mouse hippocampal neurons (r = 0.564, MSE = 13.444).
“while N2A had the lowest correlation level (r = 0.564, MSE = 13.444. Fig 4B)”
Quote in the paperSubstantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingreasoning
A larger number of miRNAs were only detected in the human tissue.
“Importantly, a larger number of miRNAs were only detected in the human tissue.”
Quote in the paperNot a substantial claim - Findingown data
200 miRNAs were detected when comparing N2A and SH-SY5Y.
“Comparing first the two neuroblast cell lines (N2A and SH-SY5Y), we found 200 miRNAs detected with 59 miRNAs with lower expression and 50 miRNAs with higher expression levels in N2A compared to SH-SY5Y (Fig 3C).”
Quote in the paperNot a substantial claim - Findingown data
miR-30b and miR-30c have similar expression levels in all four cell types (primary hippocampal neurons, HT22, N2A, SH-SY5Y).
“Here, we found several miRNAs have similar levels in all cells, for example, miR-30b and miR-30c (Fig 5A).”
Quote in the paperNot a substantial claim - Findingown data
163 miRNAs were commonly detected between primary hippocampal neurons and N2A.
“The number of commonly detected miRNAs between primary hippocampal neurons and both neuroblast cell lines was similar (163 and 166 miRNAs in N2A and SH-SY5Y respectively; Fig 3D and 3E).”
Quote in the paperNot a substantial claim - Findingown data
miR-146a had the lowest expression in HT22 or N2A.
“miR-129 was not detected in HT22 or N2A, miR-134 was not detected in HT22, miR-135a was not detected in N2A, and miR-146a had the lowest expression in HT22 or N2A (Fig 3B).”
Quote in the paperNot a substantial claim - Findingown data
In HT22 compared to primary neuronal cells, miRNAs involved in development and cell division (e.g. miR-18, miR-27a/b, miR-31, miR-106a/b and miR-222) had higher expression levels.
“while miRNAs involved in development and cell division (for example miR-18, miR-27a/b, miR-31, miR-106a/b and miR-222) had higher expression levels in HT22 than in primary neuronal cells cultures (Fig 4A).”
Quote in the paperSubstantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingown data
The expression levels of individual miRNAs in primary hippocampal neurons correlate with those in SH-SY5Y cells (r = 0.721, MSE = 8.443).
“and C) SH-SY5Y (r = 0.721, MSE = 8.443).”
Quote in the paperSubstantial claim - Findingown data
In SH-SY5Y cells, miR-27a, miR-103, and miR-140 have higher expression levels than in primary mouse hippocampal neurons.
“whereas miR-27a, miR-103 or miR-140 had a higher expression level in SH-SY5Y compared to primary cell lines.”
Quote in the paperNot a substantial claim - Findingcitation
In mouse and rat hippocampal neurons, miR-125a, miR-125b, miR-184, miR-195, miR-214 and miR-384 are in the highest expression group.
“This includes similar expression of miR-125a, miR-125b, miR-184, miR-195, miR-214 and miR-384, which in rat and mouse hippocampal neurons are in the highest expression group.”
Quote in the paperNot a substantial claim - Findingown data
miR-129 was not detected in HT22 or N2A.
“miR-129 was not detected in HT22 or N2A, miR-134 was not detected in HT22, miR-135a was not detected in N2A, and miR-146a had the lowest expression in HT22 or N2A (Fig 3B).”
Quote in the paperNot a substantial claim - Findingown data
miR-16 and miR-29 have similar expression levels between SH-SY5Y and primary hippocampal neurons.
“and miR-16 and miR-29 have similar expression levels between SH-SY5Y and neurons (Fig 5D).”
Quote in the paperNot a substantial claim - Findingown data
43% of commonly detected miRNAs between SH-SY5Y and primary hippocampal neurons were expressed at a similar level.
“From these commonly detected miRNAs, HT22 showed the highest level of similarly-expressed miRNAs, with 57% of the miRNAs expressed at a similar level, followed by SH-SY5Y cells, with 43% of miRNAs expressed at a similar level, and 38% of miRNAs expressed at a similar level between N2A and primary hippocampal neurons (Fig 3D–3F).”
Quote in the paperSubstantial claim - Findingown data
72% of detected miRNAs were commonly expressed between HT22 and N2A immortalized cell lines.
“This revealed 72% of the detected miRNAs were commonly expressed between HT22 and N2A immortalized cell lines (Fig 3G)”
Quote in the paperSubstantial claim - Findingown data
142 miRNAs were commonly detected between HT22 and primary hippocampal neurons.
“We detected 142 miRNAs commonly detected between HT22 and primary hippocampal neurons (Fig 3F).”
Quote in the paperSubstantial claim - Findingown data
50 miRNAs had higher expression in N2A compared to SH-SY5Y.
“Comparing first the two neuroblast cell lines (N2A and SH-SY5Y), we found 200 miRNAs detected with 59 miRNAs with lower expression and 50 miRNAs with higher expression levels in N2A compared to SH-SY5Y (Fig 3C).”
Quote in the paperNot a substantial claim - Findingcitation
79% of miRNAs expressed in mouse primary hippocampal neurons were also present in the RISC complex in the adult mouse hippocampus.
“We observed that 79% of miRNAs expressed in our mouse primary hippocampal neurons were also present in the RISC complex in the adult mouse hippocampus [38]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] EM Jimenez-Mateos, 2015, microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus, Sci Rep source
- Findingcitation
Mouse primary hippocampal cell cultures have a high (approximately 80%) shared profile of miRNAs with results from rat primary hippocampal cells.
“Our mouse primary hippocampal cell cultures have a high (approximately 80%) shared profile of miRNAs with results from rat primary hippocampal cells [51].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [51] M van Spronsen, 2013, Developmental and activity-dependent miRNA expression profiling in primary hippocampal neuron cultures, PLoS One source
- Findingown data
miR-125b and miR-29a have similar expression levels only between HT-22 and primary hippocampal neurons.
“MiR-125b and miR-29a have similar levels only between HT-22 and neurons (Fig 5B).”
Quote in the paperNot a substantial claim - Findingown data
SH-SY5Y cell lines have pathways related to cytokine regulation and innate immune system.
“and, finally, in SH-SY5Y cell lines has pathways related to cytokine regulation and innate immune system (S4 Fig).”
Quote in the paperNot a substantial claim - Findingown data
In HT22 compared to primary neuronal cells, miRNAs involved in neuronal function (e.g. miR-9, miR-128, miR-132, miR-135a, miR-135b) and inflammation (miR-146a, miR-212) had lower expression levels.
“When comparing HT22 cells to primary neuronal cells, miRNAs involved in neuronal function (e.g. miR-9, miR-128, miR-132, miR-135a, miR-135b) and inflammation (miR-146a, miR-212) had lower expression levels (Fig 4A)”
Quote in the paperSubstantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingown data
38% of commonly detected miRNAs between N2A and primary hippocampal neurons were expressed at a similar level.
“From these commonly detected miRNAs, HT22 showed the highest level of similarly-expressed miRNAs, with 57% of the miRNAs expressed at a similar level, followed by SH-SY5Y cells, with 43% of miRNAs expressed at a similar level, and 38% of miRNAs expressed at a similar level between N2A and primary hippocampal neurons (Fig 3D–3F).”
Quote in the paperNot a substantial claim - Findingown data
57% of commonly detected miRNAs between HT22 and primary hippocampal neurons were expressed at a similar level.
“From these commonly detected miRNAs, HT22 showed the highest level of similarly-expressed miRNAs, with 57% of the miRNAs expressed at a similar level, followed by SH-SY5Y cells, with 43% of miRNAs expressed at a similar level, and 38% of miRNAs expressed at a similar level between N2A and primary hippocampal neurons (Fig 3D–3F).”
Quote in the paperSubstantial claim - Findingown data
In N2A compared to primary cell cultures, let-7e, miR-151, miR-335 or miR-378 had higher expression levels.
“Interestingly, let-7e, miR-151, miR-335 or miR-378, which are involved in neuronal differentiation, have higher expression levels in N2A compared to primary cell cultures (Fig 4B).”
Quote in the paperNot a substantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingown data
The expression levels of individual miRNAs in primary hippocampal neurons correlate with those in N2A cells (r = 0.564, MSE = 13.444).
“B) N2A (r = 0.564, MSE = 13.444)”
Quote in the paperSubstantial claim - Findingown data
Metabolism was the main biological pathway regulated by miRNAs expressed in primary hippocampal neurons and HT22 cells.
“Metabolism was the main pathway regulated by miRNAs expressed in primary hippocampal neurons and HT22.”
Quote in the paperNot a substantial claim - Findingown data
SH-SY5Y cell profile had an intermediate correlation level with primary mouse hippocampal neurons (r = 0.715, MSE = 8.443).
“with the SH-SY5Y cell profile falling in an intermediate range (r = 0.715, MSE = 8.443. Fig 4C).”
Quote in the paperSubstantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingown data
59 miRNAs had lower expression in N2A compared to SH-SY5Y.
“Comparing first the two neuroblast cell lines (N2A and SH-SY5Y), we found 200 miRNAs detected with 59 miRNAs with lower expression and 50 miRNAs with higher expression levels in N2A compared to SH-SY5Y (Fig 3C).”
Quote in the paperNot a substantial claim - Findingown data
miR-134 was not detected in HT22.
“miR-129 was not detected in HT22 or N2A, miR-134 was not detected in HT22, miR-135a was not detected in N2A, and miR-146a had the lowest expression in HT22 or N2A (Fig 3B).”
Quote in the paperNot a substantial claim - Findingown data
RNA regulation and post-transcriptional regulation was the pathway found between primary hippocampal neurons and SH-SY5Y cells.
“And at last, RNA regulation and post-transcriptional regulation, between primary hippocampal neurons and SH-SY5Y cells (S3 Fig).”
Quote in the paperNot a substantial claim - Findingown data
Each cell line expressed a large number of the same miRNAs as are present in mouse primary hippocampal neurons.
“Specifically, each cell line expressed a large number of the same miRNAs as are present in mouse primary hippocampal neurons.”
Quote in the paperSubstantial claim - Findingown data
miR-135a was not detected in N2A.
“miR-129 was not detected in HT22 or N2A, miR-134 was not detected in HT22, miR-135a was not detected in N2A, and miR-146a had the lowest expression in HT22 or N2A (Fig 3B).”
Quote in the paperNot a substantial claim - Findingown data
In SH-SY5Y cells, miRNAs expressed in adult brain and involved in neuronal function such as miR-124, miR-134, and miR-135a/b have lower expression levels than in primary mouse hippocampal neurons.
“Here we found miRNAs expressed in adult brain and involved in neuronal function such as miR-124, miR-134 or miR-135a/b also had a lower expression level in SH-SY5Y compared to the primary cell line (Fig 4C)”
Quote in the paperSubstantial claim - Findingown data
HT22 cells had the highest correlation level with primary mouse hippocampal neurons (r = 0.735, MSE = 8.515).
“This determined that HT22 cells had the highest correlation level (r = 0.735, MSE = 8.515. Fig 4A)”
Quote in the paperSubstantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingown data
Pathways involved in calcium regulation and CREB transcription factor signalling activation are only seen in the primary cell culture.
“This revealed that pathways involved in Calcium regulation and CREB transcription factor signalling activation are only seen in the primary cell culture”
Quote in the paperSubstantial claim - Findingown data
mTOR and S6K signalling pathways are only seen in the HT22 cell line.
“while mTOR and S6K signalling pathways are only seen in HT22 cell line”
Quote in the paperNot a substantial claim - Findingcitation
In mouse and rat hippocampal neurons, miR-103, miR-130a, miR-130b, miR-134, miR-376 and miR-449 are in the group with intermediate expression.
“and miR-103, miR-130a, miR-130b, miR-134, miR-376 and miR-449 are in the group with intermediate expression [44].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] Y Benjamini, 2000, On the adaptive control of the false discovery rate in multiple testing with independent statistics, J Educ Behav Stat source
- Findingown data
166 miRNAs were commonly detected between primary hippocampal neurons and SH-SY5Y.
“The number of commonly detected miRNAs between primary hippocampal neurons and both neuroblast cell lines was similar (163 and 166 miRNAs in N2A and SH-SY5Y respectively; Fig 3D and 3E).”
Quote in the paperSubstantial claim - Findingown data
miR-106b and miR-28 have similar expression levels only between N2A and primary hippocampal neurons.
“While miR-106b and miR-28 have similar levels only between N2A and neurons (Fig 5C)”
Quote in the paperNot a substantial claim - Findingown data
In N2A compared to primary cell cultures, miR-128, miR-132 or miR-134 displayed lower expression levels.
“Similar results were obtained for N2A cells with miR-128, miR-132 or miR-134 displaying lower expression levels in N2A (Fig 4B).”
Quote in the paperNot a substantial claim- Rests on an assumption: Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
- Findingown data
86% of miRNAs were commonly detected between SH-SY5Y cell line and human tissue.
“while 86% of miRNAs were commonly detected between the SH-SY5Y cell line and human tissue (Fig 3H).”
Quote in the paperSubstantial claim - Findingown data
Among the 98 miRNAs common to all cell types, axon guidance, cell-to-cell communication, and transport of molecules were the most significantly regulated biological pathways.
“Axon guidance, cell-to-cell communication, and transport of molecules were the most significantly regulated within the 98 common miRNAs expressed in all the cell types (S3 Fig).”
Quote in the paperNot a substantial claim - Findingown data
Extracellular matrix regulation is observed only in N2A cell lines.
“extracellular matrix regulation is observed only in N2A cell lines”
Quote in the paperNot a substantial claim - Findingown data
The expression levels of individual miRNAs in primary hippocampal neurons correlate with those in HT22 cells (r = 0.700, MSE = 8.515).
“Correlations between the expression levels of the individual miRNAs between the primary hippocampal neurons and A) HT22 (r = 0.700, MSE = 8.515)”
Quote in the paperSubstantial claim - Interpretationown data
The overlap in miRNA expression across the cell lines is likely due to biological similarity rather than random chance.
“and thus the overlap in miR expression across the cell lines is likely due to biological similarity rather than random chance.”
Quote in the paperSubstantial claim - Interpretationown data
Cultured mouse neurons are a suitable proxy for the adult brain, providing a benchmark for later comparison to cell line profiles.
“Thus, cultured mouse neurons are a suitable proxy for the adult brain providing a benchmark for the later comparison to the cell line profiles.”
Quote in the paperSubstantial claim - Premisecitation
The highest expressed miRNAs in mouse cortical primary neurons are miR-124, miR-132 and miR-135b.
“However, this differed from mouse cortical primary neurons, where the highest expressed miRNAs are miR-124, miR-132 and miR-135b [9]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] TJ Nowakowski, 2013, MicroRNA-92b regulates the development of intermediate cortical progenitors in embryonic mouse brain, Proc Natl Acad Sci U S A source
- Interpretationreasoning
The inclusion of N2A and SH-SY5Y cell lines gives the fingerprint of similarities between both neuroblastoma cell lines and primary hippocampal neurons.
“Second, the inclusion of these cell lines gives the fingerprint of the similarities between both neuroblastoma cell lines and primary hippocampal neurons.”
Quote in the paperSubstantial claim - Interpretationown data
There is overall a high degree of correlation indicating these lines are suitable models for the identification of miRNA-related processes and their target genes.
“We found overall a high degree of correlation indicating these lines are suitable ‘models’ for the identification of miRNA-related processes and their target genes.”
Quote in the paperSubstantial claim - Study design and conductcitation
The study missed isomiRs and editing, which are important for miRNA function.
“We will also have missed isomiRs and editing, which are important for miRNA function [57].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [57] K Nishikura, 2016, A-to-I editing of coding and non-coding RNAs by ADARs, Nat Rev Mol Cell Biol source
- Interpretationown data
HT22, N2A and SH-SY5Y cells express miRNAs that make them suitable for the analysis of neuronal and/or brain-related processes.
“the present study reveals that HT22, N2A and SH-SY5Y cells express miRNAs that make them suitable for the analysis of neuronal and/or brain-related processes.”
Quote in the paperSubstantial claim - Interpretationown data
The conservation of miRNA profiles between human and mouse lines supports the relevance of the mouse lines for miRNA functions in human diseases.
“This supports the relevance of the mouse lines for miRNA functions in human diseases.”
Quote in the paperSubstantial claim - Premisecitation
Undifferentiated HT22 cells express low levels of cholinergic markers and glutamate receptors, in contrast to mature hippocampal neurons.
“Undifferentiated HT22 cells express low levels of cholinergic markers and glutamate receptors [25,26], in contrast to mature hippocampal neurons.”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
The brain region may influence miRNA levels.
“suggesting that the brain region may influence miRNA levels.”
Quote in the paperSubstantial claim - Interpretationreasoning
The inclusion of HT22, N2A, and SH-SY5Y cell lines enables identification of miRNA signatures that reflect tissue origin versus immortalisation.
“First, the inclusion enables the identification of miRNAs signatures that reflect tissue origin versus immortalisation.”
Quote in the paperSubstantial claim - Interpretationreasoning
HT22 cells may be suitable for analysing neuronal apoptosis regulated by miRNAs.
“Since both miRNAs are involved in regulating processes of neuronal death [52–55], HT22 cells may be suitable for analysing neuronal apoptosis regulated by miRNAs.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [52] C Parisi, 2016, MicroRNA-125b regulates microglia activation and motor neuron death in ALS, Cell Death Differ source
- cites [53] J Banzhaf-Strathmann, 2014, MicroRNA-125b induces tau hyperphosphorylation and cognitive deficits in Alzheimer’s disease, EMBO J source
- cites [54] Y-B Ouyang, 2013, Astrocyte-enriched miR-29a targets PUMA and reduces neuronal vulnerability to forebrain ischemia, Glia source
- cites [55] K Nolan, 2016, Endoplasmic reticulum stress-mediated upregulation of miR-29a enhances sensitivity to neuronal apoptosis, Eur J Neurosci source
- Classified as probably not a substantial claim. 17
- May combine two claims. 14
- The quote only partly states this claim. 2
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPrevious studies identified a set of miRNAs enriched in neurons, with expression fivefold higher than glial cells, including miR-124, miR-132 and miR-135b, while the same cells display very low expression of miR-21 and miR-146a compared to glial cells.
“This identified a set of miRNAs that are enriched in neurons, with expression fivefold higher than the glial cells, including miR-124, miR-132 and miR-135b, while the same cells display very low expression of miR-21 and miR-146a compared to glial cells [8].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [8] A Jovičić, 2013, Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes, J Neurosci source
May combine two claims.
Findingown dataSpecific miRNA levels varied between lines, with some miRNA absent, and each line varied in terms of aligning to primary neurons.
“However, specific miRNA levels varied between lines with some miRNA absent while each line varied in terms of aligning to primary neurons.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe study did not find a large effect of species, with most miRNA profiles quite conserved between human and mouse lines.
“Finally, our study did not find a large effect of species, with most miRNA profiles quite conserved between human and mouse lines.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
FindingcitationIn mouse and rat hippocampal neurons, miR-22, miR-24, miR-26, miR-29a, miR-124 and miR-129 are within the lowest expressed miRNAs.
“Furthermore, miR-22, miR-24, miR-26, miR-29a, miR-124 and miR-129, are within the lowest expressed miRNAs”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataWhile miRNA profiles show substantial overlap with primary mouse neurons, cell lines tend to express lower levels of adult-enriched miRNAs.
“A key observation in the present study was that while miRNA profiles show substantial overlap with primary mouse neurons, they tend to express lower levels of adult-enriched miRNAs.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
FindingcitationSimilar results to the 79% overlap were found when compared with human tissue.
“with similar results found when compared with human tissue [46].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [46] JD Mills, 2020, Coding and non-coding transcriptome of mesial temporal lobe epilepsy: critical role of small non-coding RNAs, Neurobiol Dis source
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningThe results provide a catalogue of miRNA expression which researchers can use to select the most appropriate cell type for basic and applied miRNA research, including for studies on epilepsy.
“The results provide a catalogue of miRNA expression which researchers can use to select the most appropriate cell type for basic and applied miRNA research, including for studies on epilepsy.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningThe study compared immortalized cell lines to mature hippocampal neurons, not to neural progenitor cells.
“And last, in the current study, we have compared immortalized cell lines to mature hippocampal neurons, and not to neural progenitor cells.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductreasoningThe OpenArray platform has a pre-selected number of miRNAs, such that the study did not capture the full repertoire of miRNAs.
“The OpenArray platform has a pre-selected number of miRNAs such that we have not captured the full repertoire of miRNAs.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenAll procedures were performed in accordance with guidelines and approved by the Research Ethics Committee of the Royal College of Surgeons in Ireland.
“All procedures were performed in accordance with the guidelines of the European Communities Council Directives (86/609/EU and 2010/63/EU) and were reviewed and approved by the Research Ethics Committee of the Royal College of Surgeons in Ireland (REC #765) under license from the Department of Health, Dublin, Ireland (B100/4524).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningThe cell lines are a better model for neurodevelopment and may retain tumor-related miRNA profiles.
“This is not surprising and suggests researchers should be wary that the cell lines are a better model for neurodevelopment and may retain tumor-related miRNA profiles.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationSH-SY5Y are neuroblastoma cells of human origin with a neuroblast-like morphology and expression of immature neuronal markers.
“SH-SY5Y are neuroblastoma cells of human origin with a neuroblast-like morphology and expression of immature neuronal markers [29].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] ZB Kaya, 2024, Optimizing SH-SY5Y cell culture: exploring the beneficial effects of an alternative media supplement on cell proliferation and viability, Sci Rep source
Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.
InterpretationreasoningThe study supports the general suitability of each cell line as well as identifying profiles which may favour the selection of one cell type over another, depending on the research question.
“Overall, the study supports the general suitability of each cell line as well as identifying profiles which may favour the selection of one cell type over another, depending on the research question.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationDifferentiated HT22 cells express higher levels of NMDAR mRNA, making them susceptible to glutamate-induced excitotoxicity.
“Differentiated HT22 cells express higher levels of N-methyl-d-aspartate receptor (NMDAR) mRNA [27], making them susceptible to glutamate-induced excitotoxicity [26].”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningDue to the difference in maturation state, it cannot be certain whether the cell lines are more similar to progenitors or mature neurons.
“The limitation here, is the difference in maturation state and we cannot be certain whether the cell lines are more similar to progenitors or mature neurons.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataCell lines were tested for mycoplasmas before experiments and results were negative for the three immortalized cell lines.
“Cell lines were tested for mycoplasmas before experiments started and results were negative for the three immortalized cell lines.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationHT22 cells are immortalized primary mouse hippocampal neuronal cells, derived from parent HT4 cells.
“HT22 cells are immortalized primary mouse hippocampal neuronal cells, derived from parent HT4 cells [22,24].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [22] BH Morimoto, 1990, Induction and expression of long- and short-term neurosecretory potentiation in a neural cell line, Neuron source
- cites [24] BH Morimoto, 1990, Excitatory amino acid uptake and N-methyl-D-aspartate-mediated secretion in a neural cell line, Proc Natl Acad Sci U S A source
May combine two claims.
Study design and conductown dataThe study only evaluated basal levels of miRNA expression and cannot be used to infer how cell line miRNA profiles may respond to stressors.
“Third, our study only evaluated the basal levels of miRNA expression and cannot be used to infer how the cell line miRNA profiles may respond to stressors.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAfter differentiation with retinoic acid and neurotrophins, SH-SY5Y cells become morphologically similar to primary neurons and express neuron-specific markers.
“After differentiation with retinoic acid and neurotrophins, SH-SY5Y cells become morphologically similar to primary neurons and express neuron-specific markers [29].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] ZB Kaya, 2024, Optimizing SH-SY5Y cell culture: exploring the beneficial effects of an alternative media supplement on cell proliferation and viability, Sci Rep source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningThe study did not include human primary (e.g. iPSC) neurons, which would provide a useful additional comparator.
“Second, we did not include human primary (e.g. iPSC) neurons which would provide a useful additional comparator.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMany human-specific miRNAs are expressed uniquely in the brain.
“There are, however, human-specific miRNAs, many of which are expressed uniquely in the brain [56]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [56] KS Kosik, 2018, Evolution of new miRNAs and cerebro-cortical development, Annu Rev Neurosci source
Probably not a substantial claim: may not pass S2 (checkable).
Interpretationnone givenThe findings provide a useful resource for experimental planning including assessing the therapeutic potential of miRNAs for neurologic diseases such as epilepsy.
“The findings provide a useful resource for experimental planning including assessing the therapeutic potential of miRNAs for neurologic diseases such as epilepsy.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationN2A is a mouse neuroblastoma cell line.
“N2A is a mouse neuroblastoma cell line, commonly used to study neuronal differentiation and used extensively to test novel cancer treatments [28].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] D Martín, 2024, Electrical pulse stimulation parameters modulate N2a neuronal differentiation, Cell Death Discov source
Classified as probably not a substantial claim.
Study design and conductcitationp-values were adjusted for multiple testing by controlling the false discovery rate according to the method of Benjamini and Hochberg.
“p-values were adjusted for multiple testing by controlling the false discovery rate (FDR) according to the method of Benjamini and Hochberg [44].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] Y Benjamini, 2000, On the adaptive control of the false discovery rate in multiple testing with independent statistics, J Educ Behav Stat source
Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningThe cellular function of interest should be the primary decision point in choosing the cellular line rather than the species origin.
“Regardless, these findings suggest that the cellular function of interest should be the primary decision point in choosing the cellular line rather than the species origin.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataThe results represent a comprehensive mapping of basal miRNA expression profiles in commonly used neuronal cell lines, which may be useful to inform choice of cell line in miRNA research on the brain.
“Together, the results represent a comprehensive mapping of the basal miRNA expression profiles in commonly used neuronal cell lines which may be useful to inform choice of cell line in miRNA research on the brain.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The extent to which HT22, N2A, and SH-SY5Y cell lines reflect primary neurons is unclear.
“The extent to which these lines reflect primary neurons remains, however, unclear.”
The paper relies on this without support.
Immortalized cell lines typically have phenotypes and patterns of gene regulation that do not reflect some neuronal characteristics and responses to stimuli.
“However, immortalized cell lines typically have a tumoral origin or have been modified to be kept cultured indefinitely, which results in phenotypes and patterns of gene regulation that do not reflect some neuronal characteristics and responses to stimuli.”
The paper relies on this without support.
Mouse primary hippocampal neurons are a suitable comparator for the miRNA profiles of HT22, N2A, and SH-SY5Y cells.
“Mouse primary hippocampal neurons were selected as a suitable comparator for the miRNA profiles of HT22, N2A and SH-SY5Y cells (Table 1).”
The paper relies on this without support.
The suitability of cell lines for neuronal miRNA studies has often neglected an assessment of their basal miRNA expression and its relevance to primary neurons or the brain.
“However, the suitability of cell lines for neuronal miRNA studies has often neglected an assessment of their basal miRNA expression and its relevance to primary neurons or the brain.”
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.
Abstract calls all 310 miRNAs shared across four cell types
MajorThe abstract says 310 miRNAs were detected in all four cell types, but the results say only 98 were common to all four; 310 is the total detected across the cell types.
“We profiled over 700 miRNAs across the lines and detected 310 miRNAs in all four cell types.”
“We detected 310 miRNAs in the four cell types (Fig 2C). Of these, 32% (98 miRNAs) were commonly detected in all the cell types.”
Reported correlations differ between text and Fig 4 caption
MajorThe text gives correlations of 0.735 for HT22 and 0.715 for SH-SY5Y, whereas the caption gives 0.700 and 0.721 for those same comparisons.
“HT22 cells had the highest correlation level (r = 0.735, MSE = 8.515. Fig 4A), while N2A had the lowest correlation level (r = 0.564, MSE = 13.444. Fig 4B), with the SH-SY5Y cell profile falling in an intermediate range (r = 0.715, MSE = 8.443. Fig 4C).”
“Figure: Fig 4 Correlations between the expression levels of the individual miRNAs between the primary hippocampal neurons and A) HT22 (r = 0.700, MSE = 8.515); B) N2A (r = 0.564, MSE = 13.444); and C) SH-SY5Y (r = 0.721, MSE = 8.443).”
Text and Fig 5 caption name different miRNAs
MinorThe text identifies miR-28 as the miRNA compared alongside miR-106b, while the Fig 5C caption identifies it as miR-26.
“While miR-106b and miR-28 have similar levels only between N2A and neurons (Fig 5C)”
“C) miR-106b and miR-26.”
Mouse hippocampus overlap is reported as both 78% and 79%
MinorThe results and discussion give different whole-number percentages for the same comparison of primary-neuron miRNAs with adult mouse hippocampal RISC-loaded miRNAs.
“we found that 78% of the expressed miRNAs in our primary mouse neurons were also among those actively loaded in the RISC in the mouse brain (Fig 1A).”
“We observed that 79% of miRNAs expressed in our mouse primary hippocampal neurons were also present in the RISC complex in the adult mouse hippocampus [38]”
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Excitatory amino acid uptake and N-methyl-D-aspartate-mediated secretion in a neural cell line
Morimoto, B. H., & Koshland, D. E. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.9.3518 · Cited by 36 · see citing works
Evolution of new miRNAs and cerebro-cortical development
Kosik, K. S., & Nowakowski, T. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-061822 · Cited by 35 · see citing works
Zampa, F., Bicker, S., & Schratt, G. M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00171 · Cited by 29 · see citing works
Electrical pulse stimulation parameters modulate N2a neuronal differentiation
Martín, D., Ruano, D., Yúfera, A., & Daza, P. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01820-y · Cited by 21 · see citing works
Leavy, A., Brennan, G. P., & Jimenez-Mateos, E. M. (2022) · Biomedicines · doi:10.3390/biomedicines10112740 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Optogenetic modeling of wake-like transcriptional progression in human SH-SY5Y neuronal cells
Yamazaki, S., Gee, W., Valekunja, U. K., & Reddy, A. B. (2026) · Scientific Reports · doi:10.1038/s41598-026-76329-8 · Cited by 1 · see citing works
Товчига, О. В., Narajczyk, M., Kozłowska-Wysocka, K., Niedziałkowski, P., Romanowski, G., & Inkielewicz‐Stępniak, I. (2026) · Molecules · doi:10.3390/molecules31162883
Catechins in stroke: multi-target mechanisms, preclinical evidence, and translational challenges
Zhang, Y., Wang, S., & Yuan, Q. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1937660
- Authors
- Murphy, R., Villegas-Salmerón, J., Sanz-Rodriguez, A., Engel, T., Mooney, C., Henshall, D. C., & Jimenez-Mateos, E. M.
- Affiliations
- Trinity College Dublin (IE)
- Royal College of Surgeons in Ireland (IE)
- University College Dublin (IE)
- Venue
- PLOS One
- Publisher
- Public Library of Science (PLoS)
- Published
- 2025-12-03
- Volume
- 20
- Issue
- 12
- Pages
- e0326401
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC12674520
- OpenAlex
- W4417035971
- Cited by
- 3
- References
- 55
- Citations by year
- 2026: 3
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Union's ‘Seventh Framework’ Programme (602130)
- Health Research Board (ILP-POR-2022-029)
- Wellcome Trust (Ph2IISF-16585)
- Taighde Éireann – Research Ireland (17/CDA/4708, 22/FFP-P/11333 and 21/RC/10294_P2)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- microRNA expression profiles, miR-124, miR-128, mouse hippocampus, in vitro neuronal model
- MeSH terms
- Animals, Cell Line, Hippocampus, Humans, Neurons, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Mice
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-06.
Cited sources are checked by gpt-6-sol.
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 ›
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