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Evolution of regulatory signatures in primate cortical neurons at cell-type resolution

ABSTRACT: Evolution of regulatory signatures in primate cortical neurons at cell-type resolution

PROVIDER: PRJNA667052 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12764816_1.fastq.gz	Fastqsanger.gz
	SRR12764816_2.fastq.gz	Fastqsanger.gz
	SRR12764817_1.fastq.gz	Fastqsanger.gz
	SRR12764817_2.fastq.gz	Fastqsanger.gz
	SRR12764818_1.fastq.gz	Fastqsanger.gz

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Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [ChIP-Seq]

Project description:Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [ChIP-Seq]

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Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [RNA-Seq]

Project description:Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [RNA-Seq]

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Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [RNA-Seq]

Project description:The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type–specific regulatory landscapes in the cortex re- main largely unexplored. Here we report epigenomic and tran- scriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome- wide profiling of the H3K27ac histone modification, we identify neuron-subtype–specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regula- tory changes are uncovered in multiple genes, including those as- sociated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a sub- stantial fraction of pan-neuronal regulatory elements undergos subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell- type–dependent gene-expression programs, and provides a re- source for further exploration of human brain evolution and function.

2020-10-03 | GSE158932 | GEO

Evolution of regulatory signatures in primate cortical neurons at cell-type resolution [ChIP-Seq]

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Evolution of regulatory signatures in primate cortical neurons at cell-type resolution.

Project description:The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type-specific regulatory landscapes in the cortex remain largely unexplored. Here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome-wide profiling of the H3K27ac histone modification, we identify neuron-subtype-specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regulatory changes are uncovered in multiple genes, including those associated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a substantial fraction of pan-neuronal regulatory elements undergoes subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell-type-dependent gene-expression programs, and provides a resource for further exploration of human brain evolution and function.

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The Birth, Distribution and Evolution of Primate Cerebral Inhibitory Neurons

Project description:Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (doi:10.1038/nrn3444, DeFelipe et al.) and recent studies have identified primate-specific neuronal populations at the molecular level(doi:10.1038/s41586-020-2781-z, Krienen et al.). However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstructed gene expression trajectories specifying inhibitory neurons spanning the neurogenic period in macaque and mouse by analyzing the transcriptomes of 250,181 cells. We find that the initial classes of inhibitory neurons generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently-identified primate-specific TAC3 striatal interneurons are specified by a unique transcriptional program in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in newborn neurons. Second, we find that multiple classes of transcriptionally-conserved olfactory-bulb bound precursors are redirected to expanded primate white matter and striatum, including a novel peristriatal class, striatum laureatum neurons, that resemble dopaminergic periglomerular cells of the olfactory bulb. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate olfactory bulb are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian inhibitory neurons and reveal multiple developmental mechanisms for neural cell type evolution.

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Evolution of regulatory signatures in primate cortical neurons at cell-type resolution

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-10-03 | GSE158934 | GEO

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Project description:This SuperSeries is composed of the following subset Series: GSE24440: Sprouting transcriptome in cortical neurons: young GSE24441: Sprouting transcriptome in cortical neurons: aged Refer to individual Series

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Single cell transcriptomics analysis of induced pluripotent stem cell-derived cortical neurons reveals frequent dual layer identity

Project description:Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.

2016-01-08 | E-GEOD-69790 | biostudies-arrayexpress

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