RRC ID 77599
Author Wang N, Langfelder P, Stricos M, Ramanathan L, Richman JB, Vaca R, Plascencia M, Gu X, Zhang S, Tamai TK, Zhang L, Gao F, Ouk K, Lu X, Ivanov LV, Vogt TF, Lu QR, Morton AJ, Colwell CS, Aaronson JS, Rosinski J, Horvath S, Yang XW.
Title Mapping brain gene coexpression in daytime transcriptomes unveils diurnal molecular networks and deciphers perturbation gene signatures.
Journal Neuron
Abstract 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.
Volume 110(20)
Pages 3318-3338.e9
Published 2022-10-19
DOI 10.1016/j.neuron.2022.09.028
PII S0896-6273(22)00867-4
PMID 36265442
PMC PMC9665885
MeSH Animals Brain Gene Regulatory Networks Huntington Disease* / genetics Mice Protein Kinase C-theta / genetics Transcriptome*
IF 14.415
Mice RBRC00757 RBRC06804