Open AccessTranscriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing
Author(s) -
Rui Mao,
Xiaoyun Zhang,
Youyong Kong,
Shi-Fang Wu,
Hai-Qin Huo,
Yue Kong,
Zhen Wang,
Yan Liu,
Zhengping Jia,
Zikai Zhou
Publication year - 2021
Publication title -
cerebral cortex
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.694
H-Index - 250
eISSN - 1460-2199
pISSN - 1047-3211
DOI - 10.1093/cercor/bhab058
Subject(s) - anaplastic lymphoma kinase , biology , transcriptome , embryonic stem cell , signal transduction , cell type , neuroscience , microbiology and biotechnology , gene , cell , gene expression , genetics , pathology , medicine , malignant pleural effusion , lung cancer
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.