Transcriptional Dynamics During Human Adipogenesis and Its Link to Adipose Morphology and Distribution
| Autor: | Mikael Rydén, Erik Arner, Christel Björk, Robin Andersson, Carsten O. Daub, Erik Ingelsson, Hideya Kawaji, Masayoshi Itoh, Piero Carninci, Alistair R. R. Forrest, Gaby Åström, Yoshihide Hayashizaki, Timo Lassmann, Jurga Laurencikiene, Niklas Mejhert, Albin Sandelin, Peter Arner, Agné Kulyté, Anna Ehrlund |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endocrinology Diabetes and Metabolism Adipose Tissue White Lipolysis Peroxisome proliferator-activated receptor Adipose tissue White adipose tissue Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Adipocyte Internal Medicine medicine Adipocytes Humans RNA Small Interfering Enhancer Transcription factor Cells Cultured Adiposity chemistry.chemical_classification Principal Component Analysis Adipogenesis Cell Differentiation Genetics/Genomes/Proteomics/Metabolomics Phenotype Cell biology 030104 developmental biology Endocrinology chemistry Diabetes Mellitus Type 2 Insulin Resistance 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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