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Diabetes. 2017 Jan;66(1):218-230. doi: 10.2337/db16-0631. Epub 2016 Nov 1.

Transcriptional Dynamics During Human Adipogenesis and Its Link to Adipose Morphology and Distribution.

Author information

1
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
2
The Bioinformatics Centre, Department of Biology, and Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
3
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.
4
RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.
5
RIKEN Preventive Medicine & Diagnosis Innovation Program, Wakō, Saitama, Japan.
6
Telethon Kids Institute and The University of Western Australia, Perth, Western Australia, Australia.
7
Department of Biosciences and Nutrition and Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
8
Molecular Epidemiology, Department of Medical Sciences, and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
9
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
10
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden erik.arner@riken.jp peter.arner@ki.se.

Abstract

White adipose tissue (WAT) can develop into several phenotypes with different pathophysiological impact on type 2 diabetes. To better understand the adipogenic process, the transcriptional events that occur during in vitro differentiation of human adipocytes were investigated and the findings linked to WAT phenotypes. Single-molecule transcriptional profiling provided a detailed map of the expressional changes of genes, enhancers, and long noncoding RNAs, where different types of transcripts share common dynamics during differentiation. Common signatures include early downregulated, transient, and late induced transcripts, all of which are linked to distinct developmental processes during adipogenesis. Enhancers expressed during adipogenesis overlap significantly with genetic variants associated with WAT distribution. Transiently expressed and late induced genes are associated with hypertrophic WAT (few but large fat cells), a phenotype closely linked to insulin resistance and type 2 diabetes. Transcription factors that are expressed early or transiently affect differentiation and adipocyte function and are controlled by several well-known upstream regulators such as glucocorticosteroids, insulin, cAMP, and thyroid hormones. Taken together, our results suggest a complex but highly coordinated regulation of adipogenesis.

PMID:
27803022
PMCID:
PMC5860264
DOI:
10.2337/db16-0631
[Indexed for MEDLINE]
Free PMC Article

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