Evolution of regulatory signatures in primate cortical neurons at cell-type resolution
| العنوان: | Evolution of regulatory signatures in primate cortical neurons at cell-type resolution |
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| المؤلفون: | John J. Ely, Alexey Kozlenkov, Michael Wegner, Marit W. Vermunt, Ke Hao, Patrick R. Hof, Eugene V. Koonin, Chet C. Sherwood, Jun-Hao Li, Eran A. Mukamel, Stella Dracheva, Pasha Apontes, Menno P. Creyghton |
| المساهمون: | Developmental Biology |
| المصدر: | Proceedings of the National Academy of Sciences of the U.S.A., 117(45), 28422-28432. National Academy of Sciences Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 45 Proceedings of the National Academy of Sciences of the United States of America |
| بيانات النشر: | National Academy of Sciences, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Epigenomics, Male, Autism Spectrum Disorder, Gene Expression, Regulatory Sequences, Nucleic Acid, Epigenesis, Genetic, Substance Misuse, Stem Cell Research - Nonembryonic - Human, Receptors, 2.1 Biological and endogenous factors, Regulatory Elements, Transcriptional, Aetiology, Cerebral Cortex, Neurons, Pediatric, Multidisciplinary, biology, Brain, Human brain, Biological Sciences, Middle Aged, Histone Code, United States Department of Veterans Affairs, Rhesus macaque, medicine.anatomical_structure, Cerebral cortex, Neurological, GABAergic, Transcriptional, Mental health, Female, Biotechnology, Primates, Cell type, Pan troglodytes, Evolution, 1.1 Normal biological development and functioning, Opioid, glutamatergic neurons, Evolution, Molecular, Glutamatergic, Genetic, Interneurons, Underpinning research, Genetics, medicine, Animals, Humans, primate evolution, Aged, Nucleic Acid, GABAergic neurons, Human Genome, Neurosciences, Molecular, Opioid-Related Disorders, Stem Cell Research, biology.organism_classification, Macaca mulatta, Regulatory Elements, United States, Brain Disorders, Good Health and Well Being, mu, H3K27ac histone modification, regulatory elements, Neuron, Transcriptome, Drug Abuse (NIDA only), Regulatory Sequences, Neuroscience, Epigenesis, Genome-Wide Association Study |
| الوصف: | Significance The cerebral cortex of the human brain is a highly complex, heterogeneous tissue that contains many cell types that are exquisitely regulated at the level of gene expression by noncoding regulatory elements, presumably in a cell-type–dependent manner. However, assessing the regulatory elements in individual cell types is technically challenging, and therefore most of the previous studies on gene regulation were performed with bulk brain tissue. Here we analyze two major types of neurons isolated from the cerebral cortex of humans, chimpanzees, and rhesus macaques, and report complex patterns of cell-type–specific evolution of the regulatory elements in numerous genes. Many genes with evolving regulation are implicated in language abilities as well as psychiatric disorders. 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59f0d2bcd58643bcd5bb53e232d7598c https://doi.org/10.1073/pnas.2011884117 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....59f0d2bcd58643bcd5bb53e232d7598c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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