Mapping brain gene coexpression in daytime transcriptomes unveils diurnal molecular networks and deciphers perturbation gene signatures.
Huntington’s disease
Parkinson’s disease
Trank1
WGCNA
bipolar disorder
coexpression
cortex
diurnal
gene
striatum
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
19 10 2022
19 10 2022
Historique:
received:
11
05
2022
revised:
16
08
2022
accepted:
22
09
2022
entrez:
20
10
2022
pubmed:
21
10
2022
medline:
25
10
2022
Statut:
ppublish
Résumé
Brain tissue transcriptomes may be organized into gene coexpression networks, but their underlying biological drivers remain incompletely understood. Here, we undertook a large-scale transcriptomic study using 508 wild-type mouse striatal tissue samples dissected exclusively in the afternoons to define 38 highly reproducible gene coexpression modules. We found that 13 and 11 modules are enriched in cell-type and molecular complex markers, respectively. Importantly, 18 modules are highly enriched in daily rhythmically expressed genes that peak or trough with distinct temporal kinetics, revealing the underlying biology of striatal diurnal gene networks. Moreover, the diurnal coexpression networks are a dominant feature of daytime transcriptomes in the mouse cortex. We next employed the striatal coexpression modules to decipher the striatal transcriptomic signatures from Huntington's disease models and heterozygous null mice for 52 genes, uncovering novel functions for Prkcq and Kdm4b in oligodendrocyte differentiation and bipolar disorder-associated Trank1 in regulating anxiety-like behaviors and nocturnal locomotion.
Identifiants
pubmed: 36265442
pii: S0896-6273(22)00867-4
doi: 10.1016/j.neuron.2022.09.028
pmc: PMC9665885
mid: NIHMS1841844
pii:
doi:
Substances chimiques
Protein Kinase C-theta
EC 2.7.11.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3318-3338.e9Subventions
Organisme : NINDS NIH HHS
ID : P30 NS062691
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS113612
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests X.W.Y. is a Scientific Advisory Board (SAB) member for Ophidion Bio and a former SAB member for Triplet Therapeutics and Mitokinin, Inc. P.L. serves as an occasional bioinformatics consultant for The Bioinformatics CRO, Inc; Vynance Technologies, LLC; and FOXO Technologies, Inc.
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