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Series GSE46077 Query DataSets for GSE46077
Status Public on Jan 01, 2014
Title Identification of Hipk2 as an essential regulator of white fat development
Organism Mus musculus
Experiment type Expression profiling by array
Summary Homeodomain interacting protein kinase 2 (Hipk2) has previously been implicated in control of several transcription factors involved in embryonic development, apoptosis, cell proliferation and tumour development1–3. Analysis of gene expression in tissues from genetically heterogeneous mouse or human populations can reveal motifs associated with the structural or functional components of the tissue, and may predict roles for genes of unknown function4,5. Here we have applied this network strategy to uncover a novel role for the Hipk2 gene in the transcriptional system controlling adipogenesis. Both in vitro and in vivo models were used to show that knockdown or loss of Hipk2 specifically inhibits white adipose cell differentiation and tissue development. In addition, loss of Hipk2 leads to induction of pockets of multilocular brown fat-like cells in remaining white adipose depots. These cells express markers of brown and beige fat such as uncoupling protein 1 (Ucp1) and transmembrane protein 26 (Tmem26), and thermogenic genes including PPAR-γ coactivator 1a (Ppargc1a), and cell death-inducing DFFA-like effector a (Cidea). These changes are accompanied by increased insulin sensitivity in Hipk2 knock-out mice and reduced high fat diet-induced weight gain, highlighting a potential role for this kinase in diseases such as diabetes and obesity. Our study underscores the versatility and power of a readily available tissue, such as skin, for network modelling of systemic transcriptional programs involved in multiple pathways, including lipid metabolism and adipogenesis.
Overall design Mammary fat pads from 115 distinct untreated 8 week old [FVB/N x Spret/Ei] x FVB/N Backcross mice
Contributor(s) Sjölund J, Pelorosso FG, Quigley DA, DelRosario R, Balmain A
Citation(s) 24785298
Submission date Apr 15, 2013
Last update date Apr 18, 2017
Contact name David Quigley
Organization name UCSF
Department Helen Diller Comprehensive Cancer Center
Lab Ashworth Lab
Street address 1450 Third St. Room 207
City San Francisco
State/province CA
ZIP/Postal code 94158
Country USA
Platforms (1)
GPL11533 [MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version]
Samples (115)
GSM1122919 RU109_1005_mammary
GSM1122920 RU109_1006_mammary
GSM1122921 RU109_1007_mammary
BioProject PRJNA197207

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE46077_RAW.tar 481.8 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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