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Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice.

Publication ,  Journal Article
Hepler, C; Shan, B; Zhang, Q; Henry, GH; Shao, M; Vishvanath, L; Ghaben, AL; Mobley, AB; Strand, D; Hon, GC; Gupta, RK
Published in: Elife
September 28, 2018

UNLABELLED: White adipose tissue (WAT) remodeling is dictated by coordinated interactions between adipocytes and resident stromal-vascular cells; however, the functional heterogeneity of adipose stromal cells has remained unresolved. We combined single-cell RNA-sequencing and FACS to identify and isolate functionally distinct subpopulations of PDGFRβ+ stromal cells within visceral WAT of adult mice. LY6C- CD9- PDGFRβ+ cells represent highly adipogenic visceral adipocyte precursor cells ('APCs'), whereas LY6C+ PDGFRβ+ cells represent fibro-inflammatory progenitors ('FIPs'). FIPs lack adipogenic capacity, display pro-fibrogenic/pro-inflammatory phenotypes, and can exert an anti-adipogenic effect on APCs. The pro-inflammatory phenotype of PDGFRβ+ cells is regulated, at least in part, by NR4A nuclear receptors. These data highlight the functional heterogeneity of visceral WAT perivascular cells, and provide insight into potential cell-cell interactions impacting adipogenesis and inflammation. These improved strategies to isolate FIPs and APCs from visceral WAT will facilitate the study of physiological WAT remodeling and mechanisms leading to metabolic dysfunction. EDITORIAL NOTE: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed.

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

September 28, 2018

Volume

7

Location

England

Related Subject Headings

  • Tetraspanin 29
  • Stromal Cells
  • Single-Cell Analysis
  • Sequence Analysis, RNA
  • Receptor, Platelet-Derived Growth Factor beta
  • Phenotype
  • Models, Biological
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

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Hepler, C., Shan, B., Zhang, Q., Henry, G. H., Shao, M., Vishvanath, L., … Gupta, R. K. (2018). Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice. Elife, 7. https://doi.org/10.7554/eLife.39636
Hepler, Chelsea, Bo Shan, Qianbin Zhang, Gervaise H. Henry, Mengle Shao, Lavanya Vishvanath, Alexandra L. Ghaben, et al. “Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice.Elife 7 (September 28, 2018). https://doi.org/10.7554/eLife.39636.
Hepler C, Shan B, Zhang Q, Henry GH, Shao M, Vishvanath L, Ghaben AL, Mobley AB, Strand D, Hon GC, Gupta RK. Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice. Elife. 2018 Sep 28;7.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

September 28, 2018

Volume

7

Location

England

Related Subject Headings

  • Tetraspanin 29
  • Stromal Cells
  • Single-Cell Analysis
  • Sequence Analysis, RNA
  • Receptor, Platelet-Derived Growth Factor beta
  • Phenotype
  • Models, Biological
  • Mice, Inbred C57BL
  • Mice
  • Male