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Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

ABSTRACT: Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

PROVIDER: PRJNA541855 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10162200.fastq.gz	Fastqsanger.gz
	SRR10162201.fastq.gz	Fastqsanger.gz
	SRR10162202.fastq.gz	Fastqsanger.gz
	SRR10162203.fastq.gz	Fastqsanger.gz
	SRR10162204.fastq.gz	Fastqsanger.gz

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Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

Project description:Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which of these changes are biologically relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains disproportionally affect oligodendrocyte function after postnatal development and are preferentially affected in the brains of autism spectrum disorder patients. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.

2019-12-20 | GSE130871 | GEO

Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients.

Project description:Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.

| S-EPMC6965079 | biostudies-literature

Real-time quantitative PCR analysis of mouse brainstem oligodendrocytes, mouse cerebellum oligodendrocytes and baboon cerebellum oligodendrocytes

Project description:Real-time quantitative PCR analysis of mouse brainstem oligodendrocytes, mouse cerebellum oligodendrocytes and baboon cerebellum oligodendrocytes

| PRJNA752773 | ENA

DNA methylation data from newly emerged queens, newly emerged workers, adult nurses, adult foragers and adult reverted nurses Honeybees (Apis mellifera)

Project description:We investigated genome-wide DNA methylation of newly emerged queens, newly emerged workers, adult nurses, adult foragers and adult reverted nurses using comprehensive high throughput arrays for relative methylation (CHARM) We used custom Nimblegen microarrays We isolated genomic DNA from newly emerged queens, newly emerged workers, adult continuous nurses, adult continuous foragers and adult reverted nurses hybridized to custom-designed Nimblegen microarrays (CHARM arrays). Multiple brains were pooled for each sample and used for the genome-wide DNA methylation analysis.

2012-09-16 | E-GEOD-36650 | biostudies-arrayexpress

Transcription profiling of rat perineuronal A2B5/OTMP+ oligodendrocytes

Project description:Oligodendrocytes are cells from the central nervous system that can be grouped into precursors, myelin-forming, and non-myelinating perineuronal. The function of perineuronal oligodendrocytes is unknown; it was suggested that they can ensheath denuded axons. We tested this hypothesis. Using cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As perineuronal, they integrate a repertoire of transcripts designed to create a cell with its own physiological agenda. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for â we speculate â a pathological eventuality. We posit that the signature molecules PDGFR-Î±Î², cytokine PDGF-CC, and the transcription factor Pea3 used â among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of perineuronal oligodendrocytes. Experiment Overall Design: Flow Cytometry was used to isolate A2B5/OTMP+ oligodendrocytes from postnatal day 7 rat brain. 4 bioloical replicates were obtained. This data can be compared to the previously submitted oligodendrocyte expression data (GSE5940).

2008-06-18 | E-GEOD-11277 | biostudies-arrayexpress

VAMP2/3-dependent membrane proteome in oligodendrocytes

Project description:Which proteins in oligodendrocytes require VAMP2/3-mediated exocytosis for membrane trafficking? We isolated primary oligodendrocytes from transgenic mice expressing oligodendrocyte-targeted botulinum toxin and littermate controls and used surface biotinylation to determine which proteins were differentially trafficked to the cell surface.

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DNA methylation data from newly emerged queens, newly emerged workers, adult nurses, adult foragers and adult reverted nurses Honeybees (Apis mellifera)

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A2B5/OTMP+ rat perineuronal oligodendrocytes

Project description:Oligodendrocytes are cells from the central nervous system that can be grouped into precursors, myelin-forming, and non-myelinating perineuronal. The function of perineuronal oligodendrocytes is unknown; it was suggested that they can ensheath denuded axons. We tested this hypothesis. Using cell-specific tags, microarray technology and bioinformatics tools to identify gene expression differences between these subpopulations allowed us to capture the genetic signature of perineuronal oligodendrocytes. Here we report that perineuronal oligodendrocytes are configured for a dual role. As perineuronal, they integrate a repertoire of transcripts designed to create a cell with its own physiological agenda. But they maintain a reservoir of untranslated transcripts encoding the major myelin proteins for – we speculate – a pathological eventuality. We posit that the signature molecules PDGFR-αβ, cytokine PDGF-CC, and the transcription factor Pea3 used – among others - to define the non-myelinating phenotype, may be critical for mounting a myelinating programme during demyelination. Harnessing this capability is of therapeutic value for diseases such as multiple sclerosis. This is the first molecular characterization of perineuronal oligodendrocytes. Keywords: developmental

2008-06-01 | GSE11277 | GEO

Accelerated evolution of oligodendrocytes in human brain

Project description:Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in oligodendrocytes and show that oligodendrocytes have undergone accelerated gene expression evolution in the human lineage. The signature of acceleration is enriched for cell type-specific expression alterations in schizophrenia. These results underscore the importance of oligodendrocytes in human brain evolution.

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Project description:The disrupted genetic mechanisms underlying neural abnormalities in Autism Spectrum Disorder remain mostly unknown and speculative. No biological marker nor genetic signature is currently available to assist with early diagnosis. We identified a blood-based gene expression signature relevant to the brain pathophysiology in autism. Also we identified genes that are differentially expressed in ASD subjects vs controls and gene modules that efficiently classify ASD and TD subjects.

2015-03-24 | GSE42133 | GEO

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