气候变化领域集成服务门户(CCPortal): Complexity and graded regulation of neuronal cell-type–specific alternative splicing revealed by single-cell RNA sequencing

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DOI	10.1073/pnas.2013056118
	Complexity and graded regulation of neuronal cell-type–specific alternative splicing revealed by single-cell RNA sequencing
	Feng H.; Moakley D.F.; Chen S.; McKenzie M.G.; Menon V.; Zhang C.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	The enormous cellular diversity in the mammalian brain, which is highly prototypical and organized in a hierarchical manner, is dictated by cell-type–specific gene-regulatory programs at the molecular level. Although prevalent in the brain, the contribution of alternative splicing (AS) to the molecular diversity across neuronal cell types is just starting to emerge. Here, we systematically investigated AS regulation across over 100 transcriptomically defined neuronal types of the adult mouse cortex using deep single-cell RNA-sequencing data. We found distinct splicing programs between glutamatergic and GABAergic neurons and between subclasses within each neuronal class. These programs consist of overlapping sets of alternative exons showing differential splicing at multiple hierarchical levels. Using an integrative approach, our analysis suggests that RNA-binding proteins (RBPs) Celf1/2, Mbnl2, and Khdrbs3 are preferentially expressed and more active in glutamatergic neurons, while Elavl2 and Qk are preferentially expressed and more active in GABAergic neurons. Importantly, these and additional RBPs also contribute to differential splicing between neuronal subclasses at multiple hierarchical levels, and some RBPs contribute to splicing dynamics that do not conform to the hierarchical structure defined by the transcriptional profiles. Thus, our results suggest graded regulation of AS across neuronal cell types, which may provide a molecular mechanism to specify neuronal identity and function that are orthogonal to established classifications based on transcriptional regulation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Alternative splicing; Graded regulation; Neuronal cell type diversity; RNA-binding proteins; Single-cell RNA-sequencing
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180316
作者单位	Department of Systems Biology, Columbia University, New York, NY 10032, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, United States; Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, United States; Department of Neurology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY 10032, United States
推荐引用方式 GB/T 7714	Feng H.,Moakley D.F.,Chen S.,等. Complexity and graded regulation of neuronal cell-type–specific alternative splicing revealed by single-cell RNA sequencing[J],2021,118(10).
APA	Feng H.,Moakley D.F.,Chen S.,McKenzie M.G.,Menon V.,&Zhang C..(2021).Complexity and graded regulation of neuronal cell-type–specific alternative splicing revealed by single-cell RNA sequencing.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Feng H.,et al."Complexity and graded regulation of neuronal cell-type–specific alternative splicing revealed by single-cell RNA sequencing".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).