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, Lin 1,2,4; Chu, Congying 1,2,4; Li, Deying 1,2,4; Gao, Chaohong 1,2,3,4; Wu, Xia 1,2,4; Yang, Zhengyi 1,2,4; Zhang, Yu 5; Xu, Junhai 6; Nyengaard, Jens Randel 3,7,8
刊名	MOLECULAR PSYCHIATRY
	2022-03-09
页码	16
ISSN号	1359-4184
DOI	10.1038/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.
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关键词	FUNCTIONAL CONNECTIVITY ; EXPRESSION ; THOUGHT ; DYSMETRIA ; COGNITION ; NETWORK ; NEUROTRANSMITTERS ; MICROSCALE ; DISORDERS ; DIVERSITY
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
内容类型	期刊论文
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.Univ Chinese Acad Sci, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Brainnetome Ctr, Inst Automat, Beijing 100190, Peoples R China 3.Univ Chinese Acad Sci, Sino Danish Ctr, 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
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.