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

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...

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Main Authors:	Lin Yang, Zihao Su, Ziwu Wang, Zhenmeiyu Li, Zicong Shang, Heng Du, Guoping Liu, Dashi Qi, Zhengang Yang, Zhejun Xu, Zhuangzhi Zhang
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-03-01
Series:	Cell Death and Disease
Online Access:	https://doi.org/10.1038/s41419-021-03552-8

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spelling	doaj-ac205f2fd3c14594a5b727b46da9f7792021-03-14T12:03:04ZengNature Publishing GroupCell Death and Disease2041-48892021-03-0112311410.1038/s41419-021-03552-8Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neuronsLin Yang0Zihao Su1Ziwu Wang2Zhenmeiyu Li3Zicong Shang4Heng Du5Guoping Liu6Dashi Qi7Zhengang Yang8Zhejun Xu9Zhuangzhi Zhang10State 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityAbstract 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.https://doi.org/10.1038/s41419-021-03552-8
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Lin Yang Zihao Su Ziwu Wang Zhenmeiyu Li Zicong Shang Heng Du Guoping Liu Dashi Qi Zhengang Yang Zhejun Xu Zhuangzhi Zhang
spellingShingle	Lin Yang Zihao Su Ziwu Wang Zhenmeiyu Li Zicong Shang Heng Du Guoping Liu Dashi Qi Zhengang Yang Zhejun Xu Zhuangzhi Zhang Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons Cell Death and Disease
author_facet	Lin Yang Zihao Su Ziwu Wang Zhenmeiyu Li Zicong Shang Heng Du Guoping Liu Dashi Qi Zhengang Yang Zhejun Xu Zhuangzhi Zhang
author_sort	Lin Yang
title	Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons
title_short	Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons
title_full	Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons
title_fullStr	Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons
title_full_unstemmed	Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons
title_sort	transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons
publisher	Nature Publishing Group
series	Cell Death and Disease
issn	2041-4889
publishDate	2021-03-01
description	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.
url	https://doi.org/10.1038/s41419-021-03552-8
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Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons

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