Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA Sequencing
| Autor: | Hai-Qin Huo, Youyong Kong, Rui Mao, Yan Liu, Zhen Wang, Zikai Zhou, Zhengping Jia, Xiaoyun Zhang, Yue Kong, Shanshan Wu |
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| Rok vydání: | 2020 |
| Předmět: |
Cognitive Neuroscience
Neurogenesis Cell Biology ALK Pathway Transcriptome 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Neural Stem Cells Pregnancy hemic and lymphatic diseases medicine Anaplastic lymphoma kinase Animals Humans Anaplastic Lymphoma Kinase RNA-Seq 030304 developmental biology Cerebral Cortex 0303 health sciences RNA Gene Expression Regulation Developmental Oncogenes Embryonic stem cell Magnetic Resonance Imaging Cell biology medicine.anatomical_structure Female Original Article Nervous System Diseases Tyrosine kinase 030217 neurology & neurosurgery Cerebral organoid Signal Transduction |
| Zdroj: | Cereb Cortex |
| ISSN: | 1460-2199 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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