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Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders
Open accessAbstract
Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer profiles, to characterize the gene regulatory landscape of two major cell classes in the human brain. We then leverage cell-type-specific regulatory landscapes to gain insight into the cellular etiology of several brain disorders. We find that Alzheimer’s disease (AD)-associated epigenetic dysregulation is linked to neurons and oligodendrocytes, whereas genetic risk factors for AD highlighted microglia, suggesting that different cell types may contribute to disease risk, via different mechanisms. Moreover, integration of glutamatergic and GABAergic regulatory maps with genetic risk factors for schizophrenia (SCZ) and bipolar disorder (BD) identifies shared (parvalbumin-expressing interneurons) and distinct cellular etiologies (upper layer neurons for BD, and deeper layer projection neurons for SCZ). Collectively, these findings shed new light on cell-type-specific gene regulatory networks in brain disorders.
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TL;DR
This paper integrates Hi–C chromosome conformation from sorted human neurons (NeuN+) and glia (NeuN−) with transcriptomic and enhancer data to map cell-type-specific 3D regulatory architecture in the brain. It uses these maps to refine the cellular etiology of Alzheimer’s disease, schizophrenia, and bipolar disorder.
Key findings
- NeuN+ and NeuN− cells show extensive cell-type-specific chromatin architecture: 287 differential FIREs (145 NeuN+, 142 NeuN−), 253 NeuN+ super-FIREs and 157 NeuN− super-FIREs with only 9 shared, and 187,674 NeuN+ versus 167,551 NeuN− promoter-based interactions.
- AD-associated epigenetic dysregulation maps to different cell classes by direction: AD hyperacetylated H3K27ac peaks were largely active in NeuN− cells and linked to 676 genes, while AD hypoacetylated peaks were largely active in NeuN+ cells and linked to 460 genes.
- AD genetic risk converged on microglia: AD SNP-based heritability was enriched in NeuN− enhancers (NeuN− p = 8.41 × 10−9; NeuN+ p = 0.205), and NeuN− H-MAGMA identified 181 AD risk genes, enriched in microglial co-expression modules upregulated in AD.
- SCZ and BD showed neuronal heritability enrichment and both mapped to Glu- and GABA-specific enhancers; risk genes shared parvalbumin-expressing interneuron (In6) enrichment, while BD showed upper-layer Ex1 specificity and SCZ showed Ex2 specificity.
Methods
- Hi–C libraries were generated from FANS-sorted NeuN+ and NeuN− nuclei from four dorsolateral prefrontal cortex (DLPFC) samples; RNA-seq was also generated from sorted nuclei, and published H3K27ac data from Glu and GABA neurons were integrated.
- Chromatin architecture was analyzed as A/B compartments, TADs, FIREs/super-FIREs, and promoter-anchored loops; cell-type-specific enhancer–promoter relationships were built by overlapping differential H3K27ac peaks with Hi–C interactions.
- Disease analyses used LDSC for SNP-based heritability enrichment and H-MAGMA to map GWAS risk variants to genes using NeuN−, Glu, or GABA regulatory maps; GWAS datasets included AD, SCZ, and BD.
Limitations
- The paper states that neuronal subtype-specific findings need verification with neuronal subtype-specific Hi–C data (e.g., Glu and GABA Hi–C) and that CRISPR/Cas9 enhancer targeting could further test risk-gene enhancer roles.
- The paper states that AD epigenetic changes may reflect either cellular composition changes or changes in regulatory landscape/cellular function, requiring future investigation.
- Evident from the text: Hi–C was based on only four DLPFC samples, and NeuN+/NeuN− fractions are broad cell classes rather than pure cell types; Glu/GABA regulatory maps were inferred by integrating subtype H3K27ac peaks with NeuN+ Hi–C rather than subtype Hi–C.
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54 Own result · 48 Not checked yet · 22 Own interpretation · 1 Supported
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In the paper
“Studies in AD have revealed changes in gene regulation manifested by differences in H3K27ac in bulk tissue38, but how this relates to cell-type-specific vulnerability is not known.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
What the sources say
- Supportedcites [38] Marzi, S. J. et al. A histone acetylome-wide association study of Alzheimer’s disease identifies disease-associated H3K27ac differences in the entorhinal cortex. Nat. Neurosci. 21, 1618–1627 (2018). source
The Discussion reports widespread AD-associated H3K27ac variation in post-mortem entorhinal cortex tissue samples and relates it to potential regulatory genomic pathways. The differential-acetylation section reports 4,162 peaks differing between AD cases and controls. These passages support the cited clause about H3K27ac differences in tissue; the subsequent statement about cell-type-specific vulnerability is not attributed to this source. (LLM, conf=0.93)
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“Genes located in common FIREs were involved in housekeeping functions (e.g., microtubule polymerization, cell junction assembly) as well as pathways that involve both neurons and oligodendrocytes (e.g., main axon, Supplementary Data 1).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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In the paper
“Among them, 1248 FIREs were shared between NeuN+ and NeuN− cells based on the coordinate-level overlap and similarities in FIRE scores (hereafter referred to as common FIREs, “Methods”, Supplementary Data 1).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“A substantial fraction of chromatin interactions were distal, as ~50% of chromatin interactions brought two genomic regions linearly separated by 320 kb or more into close proximity (Supplementary Fig. 7c) and captured complex enhancer–promoter interactions.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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“NeuN− distal enhancers were also enriched for motifs for the IRF family, such as IRF4, IRF7, IRF8, and IRF9 (Supplementary Fig. 7g), which contains key regulators of neural immune pathways expressed in glial cells31.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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“Over 75% of promoter-based interactions were detected within TADs (Supplementary Fig. 7a).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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“We found that the majority of NeuN+ and NeuN− FIREs overlapped with NeuN+ and NeuN− differential H3K27ac peaks, respectively, displaying remarkable cell-type-specificity (Fig. 1c, d).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
What the sources say
- Not checked yetcites [27] Girdhar, K. et al. Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome. Nat. Neurosci. 21, 1126–1136 (2018). source
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“TFs involved in neuronal fate commitment, including ZBTB18, SMARCC1, TBR1, and NEUROD2, were enriched in NeuN+ cells (Supplementary Fig. 7g).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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“Notably, the number of enhancers that interact with promoters was strikingly correlated with gene regulation, as gene expression linearly increased with the number of physically interacting enhancers up to a total of 10 or more (Supplementary Fig. 7e)3,28.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
What the sources say
- Not checked yetcites [3] Wang, D. et al. Comprehensive functional genomic resource and integrative model for the human brain. Science 362, eaat8464 (2018).
- Not checked yetcites [28] Kozlenkov, A. et al. Evolution of regulatory signatures in primate cortical neurons at cell-type resolution. Proc. Natl Acad. Sci. USA 117, 28422–28432 (2020). source
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“We found that NeuN− cells showed higher structural similarity with the adult brain than the fetal brain, indicative of gliogenesis in the postnatal brain20.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“Over 95% of super-FIREs overlapped with differential H3K27ac peaks and all super-FIREs overlapped with promoters, indicating that they have a particularly strong cell-type-specific regulatory impact (Supplementary Fig. 5b, c).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“We detected extensive compartment switching between NeuN+ and NeuN− cells: 4,333 regions (in 100kb resolution) switched from compartment A to B between NeuN− to NeuN+ cells, while 2098 regions switched from compartment B to A in NeuN+ to NeuN− cells.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“Only 9 super-FIREs were detected in both NeuN+ and NeuN− cells, leaving 253 and 157 cell-type-specific super-FIREs in NeuN+ and NeuN− cells, respectively (Supplementary Fig. 5a, Supplementary Data 2).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“detecting 287 differential FIREs between NeuN+ (145) and NeuN− (142) cells (hereby referred to as NeuN+ and NeuN− FIREs, respectively, Fig. 1b, Supplementary Data 2).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“We detected 3966 and 3967 FIREs in NeuN+ and NeuN− cells, respectively (Fig. 1a and Supplementary Data 1)24.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
What the sources say
- Not checked yetcites [24] Crowley, C. et al. FIREcaller: detecting frequently interacting regions from Hi-C data. Comput. Struct. Biotechnol. J. 19, 355–362 (2021). source
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“Importantly, genes located in compartments that switch from A to B between NeuN− and NeuN+ were highly expressed in oligodendrocytes and astrocytes, while those that switch from B to A in NeuN− to NeuN+ were highly expressed in neurons, suggesting that the difference in chromosome conformation between NeuN+ and NeuN− cells is associated with cell-type-specific gene regulation (Supplementary Fig. 3”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“NeuN+ super-FIREs overlapped with genes functioning in synapses and ion gated channels that were highly expressed in neurons, while NeuN− super-FIREs overlapped with genes involved in cell adhesion, myelination, and ensheathment of neurons, with high expression in glia (Supplementary Fig. 5d-f, 6).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“NeuN+ cells showed high similarity with adult brains, fetal brains, and iPSC-derived neurons.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“We detected 187,674 and 167,551 promoter-based interactions3,4 from NeuN+ and NeuN− cells, respectively (Fig. 2a).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
What the sources say
- Not checked yetcites [3] Wang, D. et al. Comprehensive functional genomic resource and integrative model for the human brain. Science 362, eaat8464 (2018).
- Not checked yetcites [4] Won, H. et al. Chromosome conformation elucidates regulatory relationships in developing human brain. Nature 538, 523–527 (2016). source
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“Roughly 37% of interactions occurred between enhancers and promoters and ~23% of interactions occurred between two different promoters (Supplementary Fig. 7b).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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“Salient examples include GRIN2B, which overlaps with a NeuN+ FIRE, and OLIG1 and OLIG2, which overlap with a NeuN− FIRE (Fig. 1e, f, Supplementary Fig. 4).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“Indeed, NeuN+ FIREs overlapped with neuronal genes that were enriched for synaptic function (Fig. 1g), while NeuN− FIREs overlapped with genes involved in myelination, glial differentiation, and oligodendrocyte differentiation (Fig. 1h).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
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“We were able to link hypoacetylated peaks in AD to 460 genes using NeuN+ Hi–C data and hyperacetylated peaks in AD to 676 genes using NeuN− Hi–C data (hereby referred to as NeuN+ hypo- and NeuN− hyperacetylated genes, respectively, Fig. 3c, Supplementary Data 5).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
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“Consistent with previous studies16,42,49, these genes were highly expressed in the postnatal brain samples (Fig. 4d) and microglia (Fig. 4e).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Genetic risk factors associated with AD converge onto microglial function
What the sources say
- Not checked yetcites [16] Nott, A. et al. Brain cell type–specific enhancer–promoter interactome maps and disease-risk association. Science 366, 1134–1139 (2019). source
- Not checked yetcites [42] Lambert, J. C. et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet. 45, 1452–1458 (2013). source
- Not checked yetcites [49] Jansen, I. E. et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat. Genet. 51, 404–413 (2019). source
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“For example, a gene that encodes a synaptic scaffolding protein, HOMER132, was engaged in NeuN+ specific peaks and loops and its expression was significantly higher in NeuN+ cells compared with NeuN− cells (Fig. 2b).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
What the sources say
- Not checked yetcites [32] Tu, J. C. et al. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21, 717–726 (1998). source
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“We obtained 45,911 Glu-specific and 32,169 GABA-specific H3K27ac peaks and assigned them to 6234 and 4342 genes, respectively (Supplementary Fig. 8a, Supplementary Data 4).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Enhancer–promoter interactions in glutamatergic and GABAergic neurons
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“Lastly, genes assigned to NeuN+ specific peaks were more highly expressed in neurons, while those assigned to NeuN− specific peaks were highly expressed in oligodendrocytes and astrocytes (Fig. 2f), demonstrating the tight relationship between cell-type-specific chromatin architecture and expression signature.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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“In line with these findings, NeuN+ enhancer–promoter interactions were enriched for synaptic and axonal genes, whereas NeuN− enhancer–promoter interactions were associated with actin-based motility (Supplementary Data 3).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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“GO analysis demonstrated that NeuN+ hypoacetylated genes included synaptic genes while NeuN− hyperacetylated genes were involved in catalytic activity and glycoprotein binding (Supplementary Data 5).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
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“Notably, the BIN1 promoter was connected to multiple enhancers in NeuN−, but not in NeuN+ cells, demonstrating the highly cell-type-specific gene regulatory landscape within the locus.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Genetic risk factors associated with AD converge onto microglial function
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“These modules were involved in transcriptional regulation and cellular proliferation and were annotated as astrocyte-specific41.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
What the sources say
- Not checked yetcites [41] Seyfried, N. T. et al. A multi-network approach identifies protein-specific co-expression in asymptomatic and symptomatic Alzheimer’s disease. Cell Syst. 4, 60–72.e4 (2017). source
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“Cellular expression profiles also confirmed these findings, as NeuN+ hypoacetylated genes were highly expressed in neurons, while NeuN− hyperacetylated genes were highly expressed in oligodendrocytes, astrocytes, and endothelial cells (Fig. 3f).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
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“In contrast, a glial gene, SOX1033, was engaged in NeuN− specific H3K27ac peaks and Hi–C loops, and had higher expression in NeuN− cells than in NeuN+ cells (Fig. 2c).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
What the sources say
- Not checked yetcites [33] Kuhlbrodt, K., Herbarth, B., Sock, E., Hermans-Borgmeyer, I. & Wegner, M. Sox10, a novel transcriptional modulator in glial cells. J. Neurosci. 18, 237–250 (1998). source
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In the paper
“AD risk genes were enriched for amyloid−beta (Aβ) pathways, lipoprotein assembly, and immune processes (Fig. 4c, Supplementary Data 6).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Genetic risk factors associated with AD converge onto microglial function
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“Genes assigned to Glu peaks were highly expressed in excitatory neurons, such as layers (L)2/3 pyramidal neurons (Ex1) and L5/6 corticothalamic projection neurons (Ex7), while genes assigned to GABA peaks were highly expressed in inhibitory neurons, such as parvalbumin-expressing GABA interneurons (In6, Supplementary Fig. 8b, the definition of Ex1–8 and In1–8 neuronal subtypes is available in”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Enhancer–promoter interactions in glutamatergic and GABAergic neurons
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In the paper
“EHD1 was both hyperacetylated and highly expressed in neurotypical NeuN− cells compared to NeuN+ cells.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
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In the paper
“We detected that AD-associated hyperacetylated peaks were largely active in NeuN− cells, while AD-associated hypoacetylated peaks were largely active in NeuN+ cells in neurotypical controls (Fig. 3b).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
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In the paper
“NeuN+ hypoacetylated genes include CACNG3, whose promoter formed a loop with a peak, which was preferentially active in NeuN+ cells and was hypoacetylated in postmortem AD brain.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
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In the paper
“GRIK4, a gene that encodes an ionotropic class of glutamate receptor36, displayed complex chromatin interactions with multiple Glu peaks. In contrast, GAD1, a gene that encodes a well-known cellular marker for inhibitory neurons37, was engaged in GABA peaks via chromatin interactions (Supplementary Fig. 8c).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Enhancer–promoter interactions in glutamatergic and GABAergic neurons
What the sources say
- Not checked yetcites [36] Szpirer, C. et al. The genes encoding the glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5) are located on separate chromosomes in human, mouse, and rat. Proc. Natl Acad. Sci. USA 91, 11849–11853 (1994). source
- Not checked yetcites [37] Erlander, M. G., Tillakaratne, N. J., Feldblum, S., Patel, N. & Tobin, A. J. Two genes encode distinct glutamate decarboxylases. Neuron 7, 91–100 (1991). source
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In the paper
“We were able to assign 10,167 and 11,242 cell-type-specific H3K27ac peaks to 7828 and 8851 genes via chromatin interactions in NeuN+ and NeuN− cells, respectively (Fig. 2a, Supplementary Data 3).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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In the paper
“Glu-BD genes were enriched for neurogenesis, cell adhesion molecules, and synapses, while GABA-BD genes were enriched for transcriptional regulation and NMDA receptor activity (Supplementary Data 7).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Refined cellular etiology of SCZ and BD
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In the paper
“It is of note that while AD-associated hyperacetylation was linked to oligodendrocyte genes and astrocyte co-expression modules, genetic risk factors for AD were mapped onto a different glial cell type, microglia.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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In the paper
“Notably, AD-associated hyperacetylation was enriched for glial enhancers that are associated with upregulation of astrocytic co-expression modules in AD, while AD-associated hypoacetylation was enriched for neuronal enhancers that potentially affect downregulation of a neuronal co-expression module in AD.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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In the paper
“obtaining 753 SCZ risk genes from Glu (hereby referred to as Glu-SCZ genes) and 624 risk genes from GABA-specific regulatory interactions integrated via H-MAGMA (GABA-SCZ genes) (Supplementary Data 7).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Refined cellular etiology of SCZ and BD
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In the paper
“The genome-wide analysis of chromosome conformation in these two cell classes captures the major known elements of 3D architecture such as compartments, FIREs, and loops, addressing the roles and impact of these different hierarchical units in cell-type-specific gene regulation.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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“Glu-SCZ genes displayed widespread expression among many Glu neuronal subclasses, with relatively higher expression signatures in L3/4 neurons (Ex2) and L5/6 corticothalamic projection neurons (Ex7).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Refined cellular etiology of SCZ and BD
What the sources say
- Not checked yetcites [8] Lake, B. B. et al. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science 352, 1586–1590 (2016). source
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In the paper
“We also identified 143 and 101 BD candidate risk genes from Glu (Glu-BD genes) and GABA (GABA-BD genes) H-MAGMA, respectively (Supplementary Data 7).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Refined cellular etiology of SCZ and BD
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In the paper
“We further refined maps of neuronal chromatin architecture by integrating Hi–C data from sorted neurons with H3K27ac peaks identified in two major neuronal subtypes, Glu and GABA neurons, which led to a successful delineation of neuronal subtype-specific regulatory relationships.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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In the paper
“Glu-SCZ genes were implicated in synaptic organization, ion channel activity, and neuron projection, while GABA-SCZ genes were associated with dendrite, axon, and hormonal response (Supplementary Data 7).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Refined cellular etiology of SCZ and BD
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In the paper
“It is also of note that common genetic risk for SCZ and BD also indicated shared pathways coalescing onto parvalbumin-positive interneurons, paralleling what has been among the most robust pathologic findings in SCZ and BD63,64.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
What the sources say
- Not checked yetcites [63] Enwright Iii, J. F. et al. Transcriptome alterations of prefrontal cortical parvalbumin neurons in schizophrenia. Mol. Psychiatry 23, 1606–1613 (2018). source
- Not checked yetcites [64] Mellios, N. et al. Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia. Biol. Psychiatry 65, 1006–1014 (2009). source
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In the paper
“The fact that NeuN+ cells show high similarity with fetal brain may reflect extensive neurogenesis at midgestation, the developmental stage at which the fetal brain was obtained22.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
What the sources say
- Not checked yetcites [22] Polioudakis, D. et al. A single-cell transcriptomic atlas of human neocortical development during mid-gestation. Neuron 103, 785–801.e8 (2019). source
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In the paper
“Together, our results confirmed that gene expression was coordinately controlled by physical interactions of promoters with enhancers, indicative of transcriptional regulators that underlie cell-type-specific gene regulation.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
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In the paper
“consistent with the previous findings that multiple enhancers can interact with one promoter3,7.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
What the sources say
- Not checked yetcites [3] Wang, D. et al. Comprehensive functional genomic resource and integrative model for the human brain. Science 362, eaat8464 (2018).
- Not checked yetcites [7] Jung, I. et al. A compendium of promoter-centered long-range chromatin interactions in the human genome. Nat. Genet. 51, 1442–1449 (2019). source
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In the paper
“Notably, we found that samples were clustered by cell types, not individuals, and showed high correlation between the same cell types from different individuals (NeuN+ = 0.95–0.97; NeuN− = 0.86-0.91; Supplementary Fig. 3a), demonstrating the reproducibility across Hi–C libraries.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
What the sources say
- Not checked yetcites [19] Yang, T. et al. HiCRep: assessing the reproducibility of Hi-C data using a stratum-adjusted correlation coefficient. Genome Res. 27, 1939–1949 (2017). source
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In the paper
“Recently, promoter interaction profiles were inferred from three types of brain cells (neurons, oligodendrocytes, and microglia) obtained from the postnatal human cerebral cortex16.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Introduction
What the sources say
- Not checked yetcites [16] Nott, A. et al. Brain cell type–specific enhancer–promoter interactome maps and disease-risk association. Science 366, 1134–1139 (2019). source
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In the paper
“These results collectively suggest that in AD brains, many neuronal genes are downregulated due to their hypoacetylation in neurons, whereas many glial genes are upregulated due to their hyperacetylation in glia.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Cell-type-specific nature of AD-associated epigenetic dysregulation
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In the paper
“which contains key regulators of neural immune pathways expressed in glial cells31.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Characteristics of chromatin interactions in NeuN+ and NeuN− cells
What the sources say
- Not checked yetcites [31] Tamura, T., Yanai, H., Savitsky, D. & Taniguchi, T. The IRF family transcription factors in immunity and Oncogenesis. Annu. Rev. Immunol. 26, 535–584 (2008). source
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In the paper
“Since genetic risk resides at the initiation of the causal chain in disease pathogenesis, this differential enrichment of genetic risk factors and epigenetic regulation underscores different expression signatures in AD with distinct cellular specificities and likely causal relationships.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Genetic risk factors associated with AD converge onto microglial function
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- Rests on an assumption: Genetic risk resides at the initiation of the causal chain in disease pathogenesis.
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In the paper
“This is consistent with recent single-cell sequencing studies identifying genetic risk enrichment and gene expression changes within microglia in AD, accompanied by significant gene expression changes in other cells, including astrocytes50–52, which is where we observe epigenetic signature enrichment.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Genetic risk factors associated with AD converge onto microglial function
What the sources say
- Not checked yetcites [50] Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019). source
- Not checked yetcites [51] Grubman, A. et al. A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat. Neurosci. 22, 2087–2097 (2019). source
- Not checked yetcites [52] Sala Frigerio, C. et al. The major risk factors for Alzheimer’s disease: age, sex, and genes modulate the microglia response to Aβ plaques. Cell Rep. 27, 1293–1306.e6 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“These results highlight the importance of obtaining cell-type-specific epigenetic landscapes in diseases.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“so this initial assignment is likely to be underpowered and inaccurate.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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In the paper
“Furthermore, these peaks were obtained from the brain homogenates, which would mask opposing interactions and obscure the cell-type-specific substrate of these changes.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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In the paper
“Here, we reasoned that neuronal subtype-specific gene regulatory networks would help refine the cellular etiology of disease and potentially identify discrete molecular neuropathology across psychiatric disorders.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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In the paper
“these findings suggest cellular substrates for molecular convergence (Ex7 and In6 are shared between two disorders) and divergence (Ex1 is BD-specific, while Ex2 is SCZ-specific) among two highly genetically correlated disorders.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Refined cellular etiology of SCZ and BD
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In the paper
“In contrast to AD in which multiple glial cells are implicated, previous work has indicated neurons as the central cell-type harboring genetic risk for the majority of psychiatric disorders3,22,46,58–61.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
What the sources say
- Not checked yetcites [3] Wang, D. et al. Comprehensive functional genomic resource and integrative model for the human brain. Science 362, eaat8464 (2018).
- Not checked yetcites [22] Polioudakis, D. et al. A single-cell transcriptomic atlas of human neocortical development during mid-gestation. Neuron 103, 785–801.e8 (2019). source
- Not checked yetcites [46] Sey, N. Y. A. et al. A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles. Nat. Neurosci. https://doi.org/10.1038/s41593-020-0603-0 (2020). source
- Not checked yetcites [58] Satterstrom, F. K. et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. https://doi.org/10.1016/j.cell.2019.12.036 (2020). source
- Not checked yetcites [59] Gandal, M. J. et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science 362, eaat8127 (2018). source
- Not checked yetcites [60] Ruzzo, E. K. et al. Inherited and de novo genetic risk for autism impacts shared networks. Cell 178, 850–866.e26 (2019). source
- Not checked yetcites [61] Skene, N. G. et al. Genetic identification of brain cell types underlying schizophrenia. Nat. Genet. 50, 825–833 (2018). source
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In the paper
“In their original work, Marzi et al.38 reported AD-associated H3K27ac peaks that are either hypo- or hyperacetylated in AD-affected individuals compared to age-matched low-pathology controls38 and linked these peaks to target genes on the basis of linear distance.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
What the sources say
- Not checked yetcites Marzi et al.38 Marzi, S. J. et al. A histone acetylome-wide association study of Alzheimer’s disease identifies disease-associated H3K27ac differences in the entorhinal cortex. Nat. Neurosci. 21, 1618–1627 (2018). source
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In the paper
“Our study provides a foundation for such future study by characterizing cell-type-specific 3D chromatin structure in the adult human brain, which we show can be used to improve our understanding of gene regulatory landscape in brain disorders.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
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The paper relies on this without support.
Changes in gene expression or histone modifications may be a consequence or compensatory in disease and not necessarily causal.
“Changes in gene expression or histone modifications may be a consequence or compensatory in disease and not necessarily causal.”
The paper relies on this without support.
How AD-associated H3K27ac changes relate to cell-type-specific vulnerability is not known.
“Studies in AD have revealed changes in gene regulation manifested by differences in H3K27ac in bulk tissue38, but how this relates to cell-type-specific vulnerability is not known.”
The paper relies on this without support.
Hi-C data from neuronal subtypes is unavailable.
“Since Hi–C data from neuronal subtypes is yet unavailable, we constructed Glu and GABA H-MAGMA maps by integrating Glu- and GABA-enhancers with NeuN+ Hi–C data, respectively (“Methods”)”
The paper relies on this without support.
Genetic risk resides at the initiation of the causal chain in disease pathogenesis.
“Since genetic risk resides at the initiation of the causal chain in disease pathogenesis, this differential enrichment of genetic risk factors and epigenetic regulation underscores different expression signatures in AD with distinct cellular specificities and likely causal relationships.”
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
“The 3D genome plays an important role in neuronal gene expression and function”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [97]
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Methods > FIRE analysis
“NeuN− differential FIREs were defined in the opposite way; NeuN− FIRE scores<qnorm (0.9) & NeuN+ FIRE scores>qnorm (0.95).”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Methods > FIRE analysis
“NeuN+ differential FIREs were identified by obtaining the genomic regions that have NeuN+ FIRE scores greater than qnorm (0.975) and NeuN− FIRE scores lower than qnorm (0.9).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Refined cellular etiology of SCZ and BD
“Ex1 is BD-specific, while Ex2 is SCZ-specific”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Discussion
“discrete cellular substrates that may contribute to difference between BD (Ex1) and SCZ (Ex5)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
“2098 regions switched from compartment B to A in NeuN+ to NeuN− cells.”
§ Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders > Results > Differential FIREs and super-FIREs are associated with cell-type-specific gene regulation
“those that switch from B to A in NeuN− to NeuN+ were highly expressed in neurons”
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Self-citationGraph-based genome alignment and genotyping with HISAT2 and HISAT-genotype
Kim, D., Paggi, J. M., Park, C., Bennett, C., & Salzberg, S. L. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0201-4 · Cited by 15,022
StringTie enables improved reconstruction of a transcriptome from RNA-seq reads
Pertea, M., Pertea, G. M., Antonescu, C. M., Chang, T.-C., Mendell, J. T., & Salzberg, S. L. (2015) · Nature Biotechnology · doi:10.1038/nbt.3122 · Cited by 14,406
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368
Self-citationREVIGO summarizes and visualizes long lists of gene ontology terms
Supek, F., Bošnjak, M., Škunca, N., & Šmuc, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021800 · Cited by 6,264
Research works printed but not linked: 1
- Stark, R. et al. DiffBind: differential binding analysis of ChIP-Seq peak data. R. Package Version 100, 4–3 (2011).
Cited by
Sorted by citations
Items 101–103 of 103
The role of oxidative stress in the pathogenesis of neuroinflammation
Sorokovikova, T., Chichanovskaya, L., Pavlova, O., Morozov, A. M., Bereza, A., & Tsurtsumia, D. (2026) · Vrach · doi:10.29296/25877305-2026-08-03 · Cited by 1
Epigenetic control of transposable elements in brain and brain disorders
Smith, C. A., & Hamilton, P. J. (2026) · Epigenetics · doi:10.1080/15592294.2026.2732514
“…provocative considering the robust body of evidence that demonstrates the highly dynamic nature of the cell types of the nervous system in terms of chromatin organization, epigenetic post-translational modifications to DNA and histones, and transcription factor expression and function [18–31].”
Dataset related to article "A chromEM-staining protocol optimized for cardiac tissue"
Musolino, E., Pagiatakis, C., Pierin, F., Sabatino, D., Finzi, G., Gornati, R., Bernardini, G., & Papait, R. (2023) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.10124696
Metadata
- Authors
- Hu, B., Won, H., Mah, W., Park, R. B., Kassim, B., Spiess, K., Kozlenkov, A., Crowley, C. A., Pochareddy, S., The PsychENCODE Consortium, Ashley-Koch, A. E., Crawford, G. E., Garrett, M. E., Song, L., Safi, A., Johnson, G. D., Wray, G. A., Reddy, T. E., Goes, F. S., Zandi, P., Bryois, J., Jaffe, A. E., Price, A. J., Ivanov, N. A., Collado-Torres, L., Hyde, T. M., Burke, E. E., Kleiman, J. E., Tao, R., Shin, J. H., Girdhar, K., Jiang, Y., Kundakovic, M., Brown, L., Wiseman, J. R., Zharovsky, E., Jacobov, R., Devillers, O., Flatow, E., Hoffman, G. E., Belmont, J., Del Valle, D., Francoeur, N., Hadjimichael, E., Pinto, D., van Bakel, H., Roussos, P., Fullard, J. F., Bendl, J., Hauberg, M. E., Charney, A. W., Haroutunian, V., Lipska, B. K., Lewis, D. A., Hahn, C.-G., Mangravite, L. M., Peters, M. A., Chae, Y., Peng, J., Niu, M., Wang, X., Webster, M. J., Beach, T. G., Chen, C., Jiang, Y., Dai, R., Wang, Y., Xia, Y., Shieh, A. W., Liu, C., Grennan, K. S., Vadukapuram, R., Giase, G., Fitzgerald, D., Cheng, L., Brown, M., Brown, M., Brunetti, T., Goodman, T., Alsayed, M., White, K. P., Ray, M., Polioudakis, D., Wamsley, B., Yin, J., De La Torre Ubieta, L., Gandal, M. J., Swarup, V., Sanders, S. J., State, M. W., Werling, D. M., An, J.-Y., Sheppard, B., Willsey, A. J., Kefi, A., Mattei, E., Purcaro, M., Weng, Z., Moore, J., Pratt, H., Huey, J., Borrman, T., Sullivan, P. F., Giusti-Rodriguez, P., Kim, Y., Szatkiewicz, J., Rhie, S. K., Armoskus, C., Camarena, A., Farnham, P. J., Spitsyna, V. N., Witt, H., Schreiner, S., Evgrafov, O. V., Knowles, J. A., Gerstein, M., Liu, S., Navarro, F. C. P., Warrell, J., Clarke, D., Emani, P. S., Gu, M., Shi, X., Xu, M., Yang, Y. T., Kitchen, R. R., Gürsoy, G., Zhang, J., Carlyle, B. C., Nairn, A. C., Li, M., Skarica, M., Li, Z., Sousa, A. M. M., Santpere, G., Choi, J., Zhu, Y., Gao, T., Miller, D. J., Cherskov, A., Yang, M., Amiri, A., Coppola, G., Mariani, J., Scuderi, S., Szekely, A., Vaccarino, F. M., Wu, F., Weissman, S., Wang, D., Roychowdhury, T., Abyzov, A., Li, Y., Dracheva, S., Sestan, N., Akbarian, S., & Geschwind, D. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Icahn School of Medicine at Mount Sinai (US)
- James J. Peters VA Medical Center (US)
- Yale University (US)
- Duke University (US)
- Johns Hopkins University (US)
- Karolinska Institutet (SE)
- Lieber Institute for Brain Development (US)
- Central South University (CN)
- National Institutes of Health (US)
- University of Pittsburgh (US)
- University of Pennsylvania (US)
- Sage Bionetworks (US)
- St. Jude Children's Research Hospital (US)
- Stanley Medical Research Institute (US)
- Banner Sun Health Research Institute (US)
- SUNY Upstate Medical University (US)
- University of Chicago (US)
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- University of Illinois Chicago (US)
- University of Massachusetts Chan Medical School (US)
- University of Southern California (US)
- SUNY Downstate Health Sciences University (US)
- University of Wisconsin–Madison (US)
- Mayo Clinic (US)
- Corresponding author
- Won, Hyejung
- Geschwind, Daniel H.
- ORCID
- Hu, Benxia
- Won, Hyejung
- Park, Royce B.
- Spiess, Keeley
- Kozlenkov, Alexey
- Crowley, Cheynna A.
- Pochareddy, Sirisha
- Crawford, Gregory E.
- Song, Lingyun
- Safi, Alexias
- Johnson, Graham D.
- Wray, Gregory A.
- Reddy, Timothy E.
- Goes, Fernando S.
- Zandi, Peter
- Bryois, Julien
- Jaffe, Andrew E.
- Price, Amanda J.
- Ivanov, Nikolay A.
- Hyde, Thomas M.
- Tao, Ran
- Shin, Joo Heon
- Girdhar, Kiran
- Jiang, Yan
- Wiseman, Jennifer R.
- Zharovsky, Elizabeth
- Hoffman, Gabriel E.
- Francoeur, Nancy
- Hadjimichael, Evi
- Pinto, Dalila
- Roussos, Panos
- Fullard, John F.
- Bendl, Jaroslav
- Hauberg, Mads E.
- Charney, Alexander W.
- Haroutunian, Vahram
- Lewis, David A.
- Mangravite, Lara M.
- Peters, Mette A.
- Peng, Junmin
- Wang, Xusheng
- Webster, Maree J.
- Beach, Thomas G.
- Chen, Chao
- Jiang, Yi
- Dai, Rujia
- Wang, Yongjun
- Xia, Yan
- Shieh, Annie W.
- Liu, Chunyu
- Giase, Gina
- Fitzgerald, Dominic
- Cheng, Lijun
- Brown, Miguel
- Brunetti, Tonya
- White, Kevin P.
- Wamsley, Brie
- Yin, Jiani
- Gandal, Michael J.
- Swarup, Vivek
- Sanders, Stephan J.
- State, Matthew W.
- Werling, Donna M.
- An, Joon-Yong
- Sheppard, Brooke
- Willsey, A. Jeremy
- Kefi, Amira
- Mattei, Eugenio
- Purcaro, Michael
- Weng, Zhiping
- Pratt, Henry
- Huey, Jack
- Borrman, Tyler
- Sullivan, Patrick F.
- Kim, Yunjung
- Szatkiewicz, Jin
- Rhie, Suhn Kyong
- Camarena, Adrian
- Farnham, Peggy J.
- Spitsyna, Valeria N.
- Witt, Heather
- Schreiner, Shannon
- Evgrafov, Oleg V.
- Knowles, James A.
- Gerstein, Mark
- Liu, Shuang
- Warrell, Jonathan
- Clarke, Declan
- Emani, Prashant S.
- Gu, Mengting
- Shi, Xu
- Xu, Min
- Yang, Yucheng T.
- Kitchen, Robert R.
- Gürsoy, Gamze
- Zhang, Jing
- Carlyle, Becky C.
- Nairn, Angus C.
- Li, Mingfeng
- Li, Zhen
- Santpere, Gabriel
- Choi, Jinmyung
- Zhu, Ying
- Gao, Tianliuyun
- Miller, Daniel J.
- Cherskov, Adriana
- Yang, Mo
- Amiri, Anahita
- Coppola, Gianfilippo
- Mariani, Jessica
- Scuderi, Soraya
- Szekely, Anna
- Vaccarino, Flora M.
- Wu, Feinan
- Wang, Daifeng
- Roychowdhury, Tanmoy
- Abyzov, Alexej
- Li, Yun
- Dracheva, Stella
- Sestan, Nenad
- Akbarian, Schahram
- Geschwind, Daniel H.
- Venue
- Nature Communications
- Published
- 2021-06-25
- Volume
- 12
- Issue
- 1
- Pages
- 3968-3968
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8233376
- OpenAlex
- W3173670503
- Semantic Scholar
- 723f2286bfab54bcc9d0127b5899e81ffa957786
- Cited by
- 103
- References
- 86
- Citations by year
- 2026: 6 · 2025: 21 · 2024: 24 · 2023: 22 · 2022: 24 · 2021: 5
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R00MH113823, DP2MH122403, P50MH106438, R01MH094714, U01MH103339, R01MH110927, R01MH100027)
- U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (R21DA051921)
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (R01AG066871)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- 3D genome organization, chromosome conformation, neurons, glia, oligodendrocytes, microglia, Alzheimer's disease, schizophrenia, bipolar disorder, enhancers, non-coding variants, parvalbumin interneurons, glutamatergic neurons, GABAergic neurons, epigenetic dysregulation
- MeSH terms
- Chromatin Immunoprecipitation Sequencing, Acetylation, Alzheimer Disease, Bipolar Disorder, Chromatin, Enhancer Elements, Genetic, Gene Expression Regulation, Histones, Humans, Lysine, Neuroglia, Neurons, Promoter Regions, Genetic, Schizophrenia, Epigenesis, Genetic, Genome-Wide Association Study, GABAergic Neurons
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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.
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