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

doi:10.1038/s41380-022-01489-8

	Uncovering the genetic profiles underlying the intrinsic organization of the human cerebellum
	Wang, Yaping 1,2,3,4; Chai, Lin2,3,4 ; Chu, Congying2,3,4 ; Li, Deying 2,3,4; Gao, Chaohong 1,2,3,4; Wu, Xia 2,3,4; Yang, Zhengyi2,3,4 ; Zhang, Yu 5; Xu, Junhai 6; Nyengaard, Jens Randel 1,7,8; Eickhoff, Simon B.9,10; Liu, Bing 11; Madsen, Kristoffer Hougaard 1,12,13; Jiang, Tianzi1,2,3,4,14 ; Fan, Lingzhong1,2,3,4,14
发表期刊	MOLECULAR PSYCHIATRY
ISSN	1359-4184
	2022-03-09
页码	16
通讯作者	Chu, Congying(chucongying@gmail.com) ; Fan, Lingzhong(lingzhong.fan@ia.ac.cn)
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.
DOI	10.1038/s41380-022-01489-8
关键词[WOS]	FUNCTIONAL CONNECTIVITY ; EXPRESSION ; THOUGHT ; DYSMETRIA ; COGNITION ; NETWORK ; NEUROTRANSMITTERS ; MICROSCALE ; DISORDERS ; DIVERSITY
收录类别	SCI
语种	英语
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
项目资助者	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
WOS研究方向	Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
WOS类目	Biochemistry & Molecular Biology ; Neurosciences ; Psychiatry
WOS记录号	WOS:000766422100003
出版者	SPRINGERNATURE
七大方向——子方向分类	脑网络分析
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/48003
专题	脑图谱与类脑智能实验室_脑网络组研究
通讯作者	Chu, Congying; Fan, Lingzhong
作者单位	1.Univ Chinese Acad Sci, Sino Danish Ctr, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100190, Peoples R China 3.Chinese Acad Sci, Brainnetome Ctr, Inst Automat, Beijing 100190, Peoples R China 4.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China 5.Zhejiang Lab, Res Ctr Healthcare Data Sci, Hangzhou 311100, Peoples R China 6.Tianjin Univ, Sch Comp Sci & Technol, Tianjin Key Lab Cognit Comp & Applicat, Tianjin 300350, Peoples R China 7.Aarhus Univ, Core Ctr Mol Morphol, Dept Clin Med, Sect Stereol & Microscopy, DK-8000 Aarhus, Denmark 8.Aarhus Univ Hosp, Dept Pathol, DK-8200 Aarhus, Denmark 9.Res Ctr Julich, Inst Neurosci & Med INM 7 Brain & Behav, D-52425 Julich, Germany 10.Heinrich Heine Univ Dusseldorf, Inst Syst Neurosci, D-40225 Dusseldorf, Germany 11.Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China 12.Tech Univ Denmark, Dept Informat & Math Modelling, DK-2800 Lyngby, Denmark 13.Copenhagen Univ Hosp Amager & Hvidovre, Ctr Funct & Diagnost Imaging & Res, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark 14.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Automat, Beijing 100190, Peoples R China
第一作者单位	模式识别国家重点实验室
通讯作者单位	模式识别国家重点实验室
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.