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Uncovering the genetic profiles underlying the intrinsic organization of the human cerebellum

文献类型：期刊论文

作者Wang, Yaping11,12,13,14; Chai, Lin11,12,13; Chu, Congying11,12,13; Li, Deying11,12,13; Gao, Chaohong11,12,13,14; Wu, Xia11,12,13; Yang, Zhengyi11,12,13; Zhang, Yu10; Xu, Junhai9; Nyengaard, Jens Randel7,8,14
刊名MOLECULAR PSYCHIATRY
出版日期2022-03-09
页码16
ISSN号1359-4184
DOI10.1038/s41380-022-01489-8
通讯作者Chu, Congying(chucongying@gmail.com) ; Fan, Lingzhong(lingzhong.fan@ia.ac.cn)
英文摘要The functional diversity of the human cerebellum is largely believed to be derived more from its extensive connections rather than being limited to its mostly invariant architecture. However, whether and how the determination of cerebellar connections in its intrinsic organization interact with microscale gene expression is still unknown. Here we decode the genetic profiles of the cerebellar functional organization by investigating the genetic substrates simultaneously linking cerebellar functional heterogeneity and its drivers, i.e., the connections. We not only identified 443 network-specific genes but also discovered that their co-expression pattern correlated strongly with intra-cerebellar functional connectivity (FC). Ninety of these genes were also linked to the FC of cortico-cerebellar cognitive-limbic networks. To further discover the biological functions of these genes, we performed a "virtual gene knock-out" by observing the change in the coupling between gene co-expression and FC and divided the genes into two subsets, i.e., a positive gene contribution indicator (GCI(+)) involved in cerebellar neurodevelopment and a negative gene set (GCI(-)) related to neurotransmission. A more interesting finding is that GCI(-) is significantly linked with the cerebellar connectivity-behavior association and many recognized brain diseases that are closely linked with the cerebellar functional abnormalities. Our results could collectively help to rethink the genetic substrates underlying the cerebellar functional organization and offer possible micro-macro interacted mechanistic interpretations of the cerebellum-involved high order functions and dysfunctions in neuropsychiatric disorders.
WOS关键词FUNCTIONAL CONNECTIVITY ; EXPRESSION ; THOUGHT ; DYSMETRIA ; COGNITION ; NETWORK ; NEUROTRANSMITTERS ; MICROSCALE ; DISORDERS ; DIVERSITY
资助项目Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project[2021ZD0200203] ; Natural Science Foundation of China[82072099] ; Natural Science Foundation of China[91432302] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB32030214] ; Youth Innovation Promotion Association ; Major Scientific Project of Zhejiang Lab[2021ND0PI01] ; NIH Blueprint for Neuroscience Research[1U54MH091657] ; McDonnell Center for Systems Neuroscience at Washington University ; Beijing Advanced Discipline Fund
WOS研究方向Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
语种英语
出版者SPRINGERNATURE
WOS记录号WOS:000766422100003
资助机构Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project ; Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Youth Innovation Promotion Association ; Major Scientific Project of Zhejiang Lab ; NIH Blueprint for Neuroscience Research ; McDonnell Center for Systems Neuroscience at Washington University ; Beijing Advanced Discipline Fund
源URL[http://ir.ia.ac.cn/handle/173211/48002]  
专题自动化研究所_脑网络组研究中心
通讯作者Chu, Congying; Fan, Lingzhong
作者单位1.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Automat, Beijing 100190, Peoples R China
2.Copenhagen Univ Hosp Amager & Hvidovre, Ctr Funct & Diagnost Imaging & Res, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark
3.Tech Univ Denmark, Dept Informat & Math Modelling, DK-2800 Lyngby, Denmark
4.Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China
5.Heinrich Heine Univ Dusseldorf, Inst Syst Neurosci, D-40225 Dusseldorf, Germany
6.Res Ctr Julich, Inst Neurosci & Med INM 7 Brain & Behav, D-52425 Julich, Germany
7.Aarhus Univ Hosp, Dept Pathol, DK-8200 Aarhus, Denmark
8.Aarhus Univ, Core Ctr Mol Morphol, Dept Clin Med, Sect Stereol & Microscopy, DK-8000 Aarhus, Denmark
9.Tianjin Univ, Sch Comp Sci & Technol, Tianjin Key Lab Cognit Comp & Applicat, Tianjin 300350, Peoples R China
10.Zhejiang Lab, Res Ctr Healthcare Data Sci, Hangzhou 311100, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Yaping,Chai, Lin,Chu, Congying,et al. Uncovering the genetic profiles underlying the intrinsic organization of the human cerebellum[J]. MOLECULAR PSYCHIATRY,2022:16.
APA Wang, Yaping.,Chai, Lin.,Chu, Congying.,Li, Deying.,Gao, Chaohong.,...&Fan, Lingzhong.(2022).Uncovering the genetic profiles underlying the intrinsic organization of the human cerebellum.MOLECULAR PSYCHIATRY,16.
MLA Wang, Yaping,et al."Uncovering the genetic profiles underlying the intrinsic organization of the human cerebellum".MOLECULAR PSYCHIATRY (2022):16.

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来源：自动化研究所

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