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Mapping brain gene coexpression in daytime transcriptomes unveils diurnal molecular networks and deciphers perturbation gene signatures.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wang, Nan 
Langfelder, Peter 
Stricos, Matthew 
Ramanathan, Lalini 
Richman, Jeffrey B 

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.

Description

Keywords

Huntington’s disease, Parkinson’s disease, Trank1, WGCNA, bipolar disorder, coexpression, cortex, diurnal, gene, striatum, Animals, Mice, Transcriptome, Protein Kinase C-theta, Gene Regulatory Networks, Huntington Disease, Brain

Journal Title

Neuron

Conference Name

Journal ISSN

0896-6273
1097-4199

Volume Title

110

Publisher

Elsevier BV