Cell type and species-specific methylation patterns in neuronal and non-neuronal cells of human and chimpanzee cortex
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431394 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6506610.fastq.gz | Fastqsanger.gz | |||
| SRR6506611.fastq.gz | Fastqsanger.gz | |||
| SRR6506612.fastq.gz | Fastqsanger.gz | |||
| SRR6506613.fastq.gz | Fastqsanger.gz | |||
| SRR6506614.fastq.gz | Fastqsanger.gz |
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Project description:Using reduced representation bisulfite sequencing (RRBS), we have compared the methylomes of neuronal and non-neuronal cells from three female human and three chimpanzee cortices (Brodmann area 10). Differentially methylated regions (DMRs) with genome-wide significance were enriched in specific chromosomal regions. Intraspecific methylation differences between neuronal and non-neuronal cells were approximately three times more abundant than interspecific methylation differences between human and chimpanzee cell types. The vast majority (>90%) of human intraspecific DMRs (including DMRs with retrotransposons) were hypomethylated in neurons, compared to glia. Intraspecific DMRs were enriched in genes that have been associated with different neuropsychiatric disorders. Interspecific DMRs were enriched in genes showing human-specific brain histone modifications. Methylation differences between human and chimpanzee non-neuronal cells (N=666) were much more frequent than neuronal interspecific DMRs (N=96). More than 95% of interspecific non-neuronal DMRs were hypermethylated in humans.
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Project description:We search for developmental changes specific to humans by examining gene expression profiles in the human, chimpanzee and rhesus macaque prefrontal and cerebellar cortex. In both brain regions, developmental patterns were more evolved in humans than in chimpanzees. The major human specific genes in prefrontal cortex was enriched in neuronal functions and regulated by several transcription factors, which were previously implicated in regulation of neuronal functions. To confirm neuronal function of the human prefrontal cortex specific genes, we identifed response genes upon neuronal activation in mouse cortical neurons. Our results show that human specific genes are enriched in the response genes upon neuronal activation, implying the function of human prefrontal cortex specific genes in synaptic development.
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Project description:We search for developmental changes specific to humans by examining gene expression profiles in the human, chimpanzee and rhesus macaque prefrontal and cerebellar cortex. In both brain regions, developmental patterns were more evolved in humans than in chimpanzees. The major human specific genes in prefrontal cortex was enriched in neuronal functions and regulated by several transcription factors, which were previously implicated in regulation of neuronal functions. To confirm neuronal function of the human prefrontal cortex specific genes, we identifed response genes upon neuronal activation in mouse cortical neurons. Our results show that human specific genes are enriched in the response genes upon neuronal activation, implying the function of human prefrontal cortex specific genes in synaptic development. The cortical neurons from E15 mouse were isolated and cultured. We then exposed neurons to bicuculline (Bic), or potassium chloride (KCl), or without treatment. The cultured neurons under each group were hybridized to Agilent whole mouse genome oligo microarray (4x44k).
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Project description:The aim of this study was to characterize the genome-wide DNA methylation profiles of chimpanzee trabecular bone samples (n=4), identify how they relate to aspects of femur bone morphology, and assess how these epigenetic patterns relate to those in other primate taxa. The Illumina Infinium MethylationEPIC array was used to assess genome-wide methylation patterns.
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Project description:We compared the genome-wide patterns of DNA methylation in the brains of humans to those of our closest evolutionary relative, chimpanzees, using base-pair resolution whole-genome methylation maps of the prefrontal cortex. Our data reveal that the prefrontal cortex is the most heavily methylated among the human tissues examined so far. Nevertheless, hundreds of genes exhibit dramatically reduced levels of promoter DNA methylation in the human brain relative to the chimpanzee brain. Many of these genes are associated with neurological disorders, psychological disorders, and cancers, and are enriched for functions related to cellular metabolic processes and protein binding. Moreover, the majority of these genes exhibit higher expression in the human brain compared to the chimpanzee brain. Profiling DNA methylation map in prefrontal cortex regions of postmortem brains of three humans and three chimpanzees
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Project description:We compared the genome-wide patterns of DNA methylation in the brains of humans to those of our closest evolutionary relative, chimpanzees, using base-pair resolution whole-genome methylation maps of the prefrontal cortex. Our data reveal that the prefrontal cortex is the most heavily methylated among the human tissues examined so far. Nevertheless, hundreds of genes exhibit dramatically reduced levels of promoter DNA methylation in the human brain relative to the chimpanzee brain. Many of these genes are associated with neurological disorders, psychological disorders, and cancers, and are enriched for functions related to cellular metabolic processes and protein binding. Moreover, the majority of these genes exhibit higher expression in the human brain compared to the chimpanzee brain.
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Project description:We performed comprehensive DNA methylation analysis in neuronal and non-neuronal nuclei obtained from the human prefrontal cortex. This revealed that neuronal and non-neuronal nuclei manifest qualitatively and quantitatively distinctive DNA methylation patterns.
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Project description:Epigenetic changes have likely contributed to the large size and enhanced cognitive abilities of the human brain which evolved within the last 2 million years after the human-chimpanzee split. Using reduced representation bisulfite sequencing, we have compared the methylomes of neuronal and non-neuronal cells from 3 human and 3 chimpanzee cortices. Differentially methylated regions (DMRs) with genome-wide significance were enriched in specific genomic regions. Intraspecific methylation differences between neuronal and non-neuronal cells were approximately 3 times more abundant than interspecific methylation differences between human and chimpanzee cell types. The vast majority (>90%) of human intraspecific DMRs (including DMRs in retrotransposons) were hypomethylated in neurons, compared with glia. Intraspecific DMRs were enriched in genes associated with different neuropsychiatric disorders. Interspecific DMRs were enriched in genes showing human-specific brain histone modifications. Human-chimpanzee methylation differences were much more frequent in non-neuronal cells (n. DMRs = 666) than in neurons (n. DMRs = 96). More than 95% of interspecific DMRs in glia were hypermethylated in humans. Although without an outgroup we cannot assign whether a change in methylation occurred in the human or chimpanzee lineage, our results are consistent with a wave of methylation affecting several hundred non-neuronal genes during human brain evolution.
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This model is described in the article:
A community-driven global reconstruction of human metabolism.
Thiele I, et al
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Nature Biotechnology
Abstract:
Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven,
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facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
This model is hosted on BioModels Database
and identified by: MODEL1310110033
.
To cite BioModels Database, please use: BioModels Database: An enhanced,
curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer
to CC0 Public Domain Dedication
for more information.
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