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

Chelsea Hepler, Bo Shan, Qianbin Zhang, Gervaise H. Henry, Mengle Shao, Lavanya Vishvanath, Alexandra L. Ghaben, Angela B. Mobley, Douglas W Strand, Gary Hon, Rana K Gupta

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Original languageEnglish (US)
JournaleLife
Volume7
DOIs
StatePublished - Sep 28 2018

Fingerprint

Intra-Abdominal Fat
White Adipose Tissue
Tissue
Stromal Cells
Adipocytes
Cytoplasmic and Nuclear Receptors
RNA Sequence Analysis
Phenotype
Adipogenesis
Peer Review
RNA
Cell Communication
Blood Vessels
Inflammation

Keywords

  • adipogenesis
  • adipose tissue
  • fibrosis
  • human biology
  • inflammation
  • medicine
  • mouse
  • mural cells
  • obesity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice. / Hepler, Chelsea; Shan, Bo; Zhang, Qianbin; Henry, Gervaise H.; Shao, Mengle; Vishvanath, Lavanya; Ghaben, Alexandra L.; Mobley, Angela B.; Strand, Douglas W; Hon, Gary; Gupta, Rana K.

In: eLife, Vol. 7, 28.09.2018.

Research output: Contribution to journalArticle

Hepler, Chelsea ; Shan, Bo ; Zhang, Qianbin ; Henry, Gervaise H. ; Shao, Mengle ; Vishvanath, Lavanya ; Ghaben, Alexandra L. ; Mobley, Angela B. ; Strand, Douglas W ; Hon, Gary ; Gupta, Rana K. / Identification of functionally distinct fibro-inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice. In: eLife. 2018 ; Vol. 7.
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