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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 [RNA-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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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.

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