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Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing

文献类型：期刊论文

作者Mao, Rui1,2; Zhang, Xiaoyun3,4; Kong, Youyong5; Wu, Shanshan6,7; Huo, Hai-qin6,7; Kong, Yue2; Wang, Zhen3; Liu, Yan6,7; Jia, Zhengping8,9; Zhou, Zikai1,3,4,10
刊名CEREBRAL CORTEX
出版日期2021-08-01
卷号31期号:8页码:3911-3924
ISSN号1047-3211
关键词anaplastic lymphoma kinase cerebral organoid neurodevelopment neural progenitor cell single-cell RNA sequencing
DOI10.1093/cercor/bhab058
通讯作者Liu, Yan(yanliu@njmu.edu.cn) ; Jia, Zhengping(zhengping.jia@sickkids.ca) ; Zhou, Zikai(zhouzikai@simm.ac.cn)
英文摘要Precise regulation of embryonic neurodevelopment is crucial for proper structural organization and functioning of the adult brain. The key molecular machinery orchestrating this process remains unclear. Anaplastic lymphoma kinase (ALK) is an oncogenic receptor-type protein tyrosine kinase that is specifically and transiently expressed in developing nervous system. However, its role in the mammalian brain development is unknown. We found that transient embryonic ALK inactivation caused long-lasting abnormalities in the adult mouse brain, including impaired neuronal connectivity and cognition, along with delayed neuronal migration and decreased neuronal proliferation during neurodevelopment. scRNA-seq on human cerebral organoids revealed a delayed transition of cell-type composition. Molecular characterization identified a group of differentially expressed genes (DEGs) that were temporally regulated by ALK at distinct developmental stages. In addition to oncogenes, many DEGs found by scRNA-seq are associated with neurological or neuropsychiatric disorders. Our study demonstrates a pivotal role of oncogenic ALK pathway in neurodevelopment and characterized cell-type-specific transcriptome regulated by ALK for better understanding mammalian cortical development.
WOS关键词ANAPLASTIC LYMPHOMA KINASE ; RECEPTOR TYROSINE KINASE ; NEURAL STEM-CELLS ; ACTIVATING MUTATIONS ; CEREBRAL ORGANOIDS ; BRAIN ORGANOIDS ; DNA-DAMAGE ; IDENTIFICATION ; PROLIFERATION ; SPECIFICATION
资助项目National Natural Science Foundation of China[81971022] ; National Natural Science Foundation of China[81471301] ; Canadian Institutes of Health Research (CIHR)[MOP119421] ; Canadian Institutes of Health Research (CIHR)[PJT155959] ; Canadian Natural Science and Engineering Research CouncilNSERC[RGPIN341498] ; Canadian Natural Science and Engineering Research CouncilNSERC[RGPIN06295] ; National Key Research and Development Program of China[2016YFC1306703] ; Jiangsu Outstanding Young Investigator Program[BK20160044] ; Program of Shanghai Academic Research Leader[19XD1423300] ; Shanghai Municipal Education Commission-Gaofeng Clinical Medicine[20191835] ; Science and Technology Commission of Shanghai Municipality[201409002600] ; Shanghai Mental Health Center-Clinical Research Center[CRC2019ZD01]
WOS研究方向Neurosciences & Neurology
语种英语
出版者OXFORD UNIV PRESS INC
WOS记录号WOS:000674446400024
源URL[http://119.78.100.183/handle/2S10ELR8/296712]  
专题中国科学院上海药物研究所
通讯作者Liu, Yan; Jia, Zhengping; Zhou, Zikai
作者单位1.Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Sch Med, Shanghai 200030, Peoples R China
2.Southeast Univ, Sch Life Sci & Technol, Nanjing 210096, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery & Dev, Zhongshan 528400, Peoples R China
5.Southeast Univ, Sch Comp Sci & Engn, Nanjing 210096, Peoples R China
6.Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211166, Peoples R China
7.Nanjing Med Univ, Sch Pharm, Inst Stem Cell & Neural Regenerat, Nanjing 211166, Peoples R China
8.Hosp Sick Children, Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada
9.Univ Toronto, Fac Med, Dept Physiol, Toronto, ON M5S 1A8, Canada
10.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Peoples R China
推荐引用方式
GB/T 7714		 Mao, Rui,Zhang, Xiaoyun,Kong, Youyong,et al. Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing[J]. CEREBRAL CORTEX,2021,31(8):3911-3924.
APA Mao, Rui.,Zhang, Xiaoyun.,Kong, Youyong.,Wu, Shanshan.,Huo, Hai-qin.,...&Zhou, Zikai.(2021).Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing.CEREBRAL CORTEX,31(8),3911-3924.
MLA Mao, Rui,et al."Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing".CEREBRAL CORTEX 31.8(2021):3911-3924.

入库方式： OAI收割

来源：上海药物研究所

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