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Epigenetic Regulation of Neuregulin-1 Tunes White Adipose Stem Cell Differentiation

24 Pages Posted: 13 Jan 2020 Sneak Peek Status: Review Complete

See all articles by Alyssa D. Cordero

Alyssa D. Cordero

American University - Department of Biology

Evan C. Callihan

American University - Department of Biology

Rana Said

American University - Department of Biology

Yasir Alowais

American University - Department of Biology

Emily S. Paffhausen

American University - Department of Biology

John Bracht

American University - Department of Biology

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Abstract

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

Suggested Citation

Cordero, Alyssa D. and Callihan, Evan C. and Said, Rana and Alowais, Yasir and Paffhausen, Emily S. and Bracht, John, Epigenetic Regulation of Neuregulin-1 Tunes White Adipose Stem Cell Differentiation. ISCIENCE-D-19-01514. Available at SSRN: https://ssrn.com/abstract=3517531 or http://dx.doi.org/10.2139/ssrn.3517531
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Alyssa D. Cordero

American University - Department of Biology ( email )

United States

Evan C. Callihan

American University - Department of Biology ( email )

United States

Rana Said

American University - Department of Biology ( email )

United States

Yasir Alowais

American University - Department of Biology ( email )

United States

Emily S. Paffhausen

American University - Department of Biology ( email )

United States

John Bracht (Contact Author)

American University - Department of Biology ( email )

United States

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