Myeloid specific ASXL2 deletion limits diet induced obesity by regulating energy expenditure
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ABSTRACT:
PROVIDER: PRJNA602939 | ENA |
REPOSITORIES: ENA
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Project description:We previously reported that global deletion of the Enhancer of Trithorax and Polycomb (ETP) gene, Asxl2, attenuates osteoclast differentiation and also completely protects mice from HFD-induced weight gain. To determine role of this gene specifically in myeloid compartment, ASXL2flox mice were bred with LysM cre (Asxl2LysM). Bone marrow-derived macrophages (BMM) were cultured for 2 days with or without Rank-ligand (RANKL). We characterized the transcriptomic profiles of BMMs and osteoclast by performing unbiased RNA-sequencing. The expression profiles of both macrophages and osteoclast was significantly distinct between two genotypes. In particular, Enrichr analysis of differentially expressed genes (DEG) reveals substantial downregulation of those associated with extracellular matrix (ECM) organization, collagen formation, cytokine-cytokine interaction and inflammatory response including genes encoding TNFα, MMPs and CXCLs, in Asxl2LysM BMMs. In contrast, cell cycle and mitosis related genes are upregulated. The fact that most of the dominant downregulated genes are also implicated in modulating adipose tissue inflammation and fibrosis, supports the concept that genetic deletion of ASXL2, in myeloid cells, may modify obesity.
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2013-06-20 | E-GEOD-43575 | biostudies-arrayexpress
Project description:Prader-Willi syndrome (PWS), a genetic cause of childhood obesity, is characterized by intellectual disabilities and sleep abnormalities. PWS-causing deletions include a neuronal long, non-coding RNA (lncRNA) processed into small nucleolar RNAs and a spliced lncRNA,116HG. We show that 116HG forms a subnuclear RNA cloud that co-purifies with the transcriptional activator RBBP5 and active metabolic genes, remains tethered to the site of its transcription and increases in size in postnatal neurons. Snord116del mice lacking 116HG exhibited increased energy expenditure corresponding to dysregulation of diurnally expressed Mtor and circadian genes Clock, Cry1, and Per2. Genomic and metabolic analyses demonstrate altered diurnal energy regulation in the Snord116del mouse cortex and link the loss of 116HG to the energy imbalance observed in PWS.
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