Epigenetic Regulation of Neuregulin-1 Tunes White Adipose Stem Cell Differentiation
24 Pages Posted: 13 Jan 2020 Sneak Peek Status: Review CompleteMore...
Expansion of subcutaneous adipose tissue by differentiation of new adipocytes has been linked to improvements in metabolic health. However, an expandability limit has been observed wherein new adipocytes cannot be produced, the existing adipocytes become enlarged (hypertrophic) and lipids spill over into ectopic sites. Inappropriate ectopic storage of these surplus lipids in liver, muscle, and visceral depots has been linked with metabolic dysfunction. Here we show that Neuregulin-1 (NRG1) serves as a master regulator of differentiation in subcutaneous primary human stem cells. We further demonstrate that DNA methylation modulates NRG1 expression in these cells, and a 3-day exposure of stem cells to a recombinant NRG1 peptide fragment is sufficient to reprogram adipogenic cellular differentiation to higher levels. These results uncover a novel molecular rheostat that constitutes a regulatory mechanism for adipose expandability, with potentially high clinical significance for human health.
Keywords: NRG1, adipose expandability, adipocytes, Diabetes
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