中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Organoid single-cell genomic atlas uncovers human-specific features of brain development

文献类型:期刊论文

作者Kanton, Sabina2; Boyle, Michael James2; He, Zhisong2; Santel, Malgorzata2; Weigert, Anne2; Sanchis-Calleja, Fatima2,3; Sidow, Leila2; Khaitovich, Philipp2,4; Paabo, Svante2; Treutlein, Barbara2,3
刊名NATURE
出版日期2019
卷号574期号:7778页码:418+
ISSN号0028-0836
关键词Silver carp oil emulsion properties microencapsulation spray drying oxidative stability
DOI10.1038/s41586-019-1654-9
文献子类Article
英文摘要The human brain has undergone substantial change since humans diverged from chimpanzees and the other great apes(1,2). However, the genetic and developmental programs that underlie this divergence are not fully understood. Here we have analysed stem cell-derived cerebral organoids using single-cell transcriptomics and accessible chromatin profiling to investigate gene-regulatory changes that are specific to humans. We first analysed cell composition and reconstructed differentiation trajectories over the entire course of human cerebral organoid development from pluripotency, through neuroectoderm and neuroepithelial stages, followed by divergence into neuronal fates within the dorsal and ventral forebrain, midbrain and hindbrain regions. Brain-region composition varied in organoids from different iPSC lines, but regional gene-expression patterns remained largely reproducible across individuals. We analysed chimpanzee and macaque cerebral organoids and found that human neuronal development occurs at a slower pace relative to the other two primates. Using pseudotemporal alignment of differentiation paths, we found that human-specific gene expression resolved to distinct cell states along progenitor-to-neuron lineages in the cortex. Chromatin accessibility was dynamic during cortex development, and we identified divergence in accessibility between human and chimpanzee that correlated with human-specific gene expression and genetic change. Finally, we mapped human-specific expression in adult prefrontal cortex using single-nucleus RNA sequencing analysis and identified developmental differences that persist into adulthood, as well as cell-state-specific changes that occur exclusively in the adult brain. Our data provide a temporal cell atlas of great ape forebrain development, and illuminate dynamic gene-regulatory features that are unique to humans.
学科主题Biochemistry & Molecular Biology ; Cell Biology
WOS关键词PLURIPOTENT STEM-CELLS ; CEREBRAL ORGANOIDS ; DIVERSITY ; EVOLUTION ; PRIMATE ; DNA ; ACCESSIBILITY ; EXPRESSION ; SEQUENCES ; CHROMATIN
语种英语
CSCD记录号CSCD:31619793
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000490988300068
版本出版稿
源URL[http://202.127.25.144/handle/331004/781]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Inst Mol & Clin Ophthalmol, Basel, Switzerland,
2.Max Planck Inst Evolutionary Anthropol, Leipzig, Germany;
3.Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland;
4.CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, Shanghai, Peoples R China;
5.Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany;
6.Skolkovo Inst Sci & Technol, Ctr Neurobiol & Brain Restorat, Moscow, Russia;
推荐引用方式
GB/T 7714
Kanton, Sabina,Boyle, Michael James,He, Zhisong,et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development[J]. NATURE,2019,574(7778):418+.
APA Kanton, Sabina.,Boyle, Michael James.,He, Zhisong.,Santel, Malgorzata.,Weigert, Anne.,...&,.(2019).Organoid single-cell genomic atlas uncovers human-specific features of brain development.NATURE,574(7778),418+.
MLA Kanton, Sabina,et al."Organoid single-cell genomic atlas uncovers human-specific features of brain development".NATURE 574.7778(2019):418+.

入库方式: OAI收割

来源:上海营养与健康研究所

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