Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells
文献类型：期刊论文
| 作者 | Li, Yuanyuan2; Wang, Ran2; Peng, Guangdun2; Zhang, Ke2; Jing, Naihe2; Qiao, Nan3; Han, Jing-Dong J.3; Tang, Ke4; Jing, Naihe1; , |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2017 |
| 卷号 | 292期号:48页码:19590-19604 |
| 关键词 | embryonic stem cell human neurodevelopment neurodifferentiation transcriptomics |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M117.796383 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| 学科主题 | Biochemistry & Molecular Biology |
| 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 |
| 语种 | 英语 |
| WOS记录号 | WOS:000416911300005 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1116]  |
| 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.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China, 2.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; 3.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; 4.Nanchang Univ, Inst Life Sci, Nanchang 330031, Jiangxi, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Yuanyuan,Wang, Ran,Peng, Guangdun,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.,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. |
入库方式： OAI收割
来源：上海营养与健康研究所
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