Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons

Lin Yang; Zihao Su; Ziwu Wang; Zhenmeiyu Li; Zicong Shang; Heng Du; Guoping Liu; Dashi Qi; Zhengang Yang; Zhejun Xu; Zhuangzhi Zhang

doi:10.1038/s41419-021-03552-8

Cell Death and Disease (Mar 2021)

Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons

Lin Yang,
Zihao Su,
Ziwu Wang,
Zhenmeiyu Li,
Zicong Shang,
Heng Du,
Guoping Liu,
Dashi Qi,
Zhengang Yang,
Zhejun Xu,
Zhuangzhi Zhang

Affiliations

Lin Yang: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Zihao Su: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Ziwu Wang: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Zhenmeiyu Li: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Zicong Shang: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Heng Du: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Guoping Liu: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Dashi Qi: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Zhengang Yang: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Zhejun Xu: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University
Zhuangzhi Zhang: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, MOE Frontier Research Center for Brain Science, Shanghai Key Lab of Birth Defect, Children’s Hospital, Fudan University

DOI: https://doi.org/10.1038/s41419-021-03552-8
Journal volume & issue: Vol. 12, no. 3
pp. 1 – 14

Abstract

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Abstract The striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allows us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington’s disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which were verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.

Published in Cell Death and Disease

ISSN: 2041-4889 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/cddis/index.html

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