Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells
Li, Yuanyuan1; Wang, Ran1; Qiao, Nan2; Peng, Guangdun1; Zhang, Ke1; Tang, Ke3; Han, Jing-Dong J.2; Jing, Naihe1,4
2017-12
发表期刊JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
卷号292期号:48页码:19590-19604
发表状态已发表
DOI10.1074/jbc.M117.796383
摘要Proper neural commitment is essential for ensuring the appropriate development of the human brain and for preventing neurodevelopmental diseases such as autism spectrum disorders, schizophrenia, and intellectual disorders. However, the molecular mechanisms underlying the neural commitment in humans remain elusive. Here, we report the establishment of a neural differentiation system based on human embryonic stem cells (hESCs) and on comprehensive RNA sequencing analysis of transcriptome dynamics during early hESC differentiation. Using weighted gene co-expression network analysis, we reveal that the hESC neurodevelopmental trajectory has five stages: pluripotency (day 0); differentiation initiation (days 2, 4, and 6); neural commitment (days 8-10); neural progenitor cell proliferation (days 12, 14, and 16); and neuronal differentiation (days 18, 20, and 22). These stages were characterized by unique module genes, which may recapitulate the early human cortical development. Moreover, a comparison of our RNA-sequencing data with several other transcriptome profiling datasets from mice and humans indicated that Module 3 associated with the day 8-10 stage is a critical window of fate switch from the pluripotency to the neural lineage. Interestingly, at this stage, no key extrinsic signals were activated. In contrast, using CRISPR/Cas9-mediated gene knockouts, we also found that intrinsic hub transcription factors, including the schizophrenia-associated SIX3 gene and septo-optic dysplasia-related HESX1 gene, are required to program hESC neural determination. Our results improve the understanding of the mechanism of neural commitment in the human brain and may help elucidate the etiology of human mental disorders and advance therapies for managing these conditions.
关键词embryonic stem cell human neurodevelopment neurodifferentiation transcriptomics
收录类别SCI ; EI
语种英语
资助项目National Natural Science Foundation of China[31430058] ; National Natural Science Foundation of China[31571513] ; National Natural Science Foundation of China[31630043] ; National Natural Science Foundation of China[91519314] ; National Natural Science Foundation of China[31661143042]
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:000416911300005
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号20174904503961
EI主题词Brain ; Cell growth ; Cell proliferation ; Cells ; Diseases ; Gene expression ; Genes ; RNA ; Stem cells ; Transcription
EI分类号Bioengineering and Biology:461
WOS关键词CEREBRAL-CORTEX DEVELOPMENT ; SEPTO-OPTIC DYSPLASIA ; MOUSE EMBRYO ; NEURAL-STEM ; HUMAN NEUROECTODERM ; HESX1 MUTATIONS ; HUMAN BRAIN ; DIRECTED DIFFERENTIATION ; CLINICAL SPECTRUM ; GENE-FUNCTION
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/14298
专题生命科学与技术学院_特聘教授组_景乃禾组
通讯作者Jing, Naihe
作者单位1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Biol Sci, Chinese Acad Sci Key Lab Computat Biol, Chinese Acad Sci Max Planck Partner Inst Computat, 320 Yue Yang Rd, Shanghai 200031, Peoples R China
3.Nanchang Univ, Inst Life Sci, Nanchang 330031, Jiangxi, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China
通讯作者单位生命科学与技术学院
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Li, Yuanyuan,Wang, Ran,Qiao, Nan,et al. Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292(48):19590-19604.
APA Li, Yuanyuan.,Wang, Ran.,Qiao, Nan.,Peng, Guangdun.,Zhang, Ke.,...&Jing, Naihe.(2017).Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells.JOURNAL OF BIOLOGICAL CHEMISTRY,292(48),19590-19604.
MLA Li, Yuanyuan,et al."Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells".JOURNAL OF BIOLOGICAL CHEMISTRY 292.48(2017):19590-19604.
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