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Cited by 346Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

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

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Hepler, Chelsea, Shan, Bo, Zhang, Qianbin, Henry, Gervaise H, Shao, Mengle, Vishvanath, Lavanya, Ghaben, Alexandra L, Mobley, Angela B +3 more·2018·eLife
DOI 10.7554/elife.39636PMC PMC6167054
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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 (see decision letter).

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  • scRNA-seq has been used to characterize dynamics of cell populations underlying adipose tissue remodeling, focusing on cell types within stromal vascular fractions, particularly preadipocytes.

    “scRNA-seq has been used to characterize the dynamics of cell populations underlying adipose tissue remodeling, with a focus on the cell types within stromal vascular fractions, particularly preadipocytes (Schwalie et al., 2018; Burl et al., 2018; Hepler et al., 2018; Merrick et al., 2019).”

    From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Hepler et al., 2018

    The Results section on single-cell RNA sequencing identifies distinct stromal populations in visceral adipose tissue, including committed preadipocytes. The Results section on high-fat-diet feeding reports changes in the frequencies of those populations during tissue remodeling, but those changes were assessed separately rather than by scRNA-seq. The source therefore supports the focus on precursor populations and remodeling, but not the claim that scRNA-seq itself characterized their dynamics. (LLM, conf=0.84)

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  • APC2 exhibited higher expression of fibrotic genes such as Fn1 and Loxl1, resembling fibro-inflammatory progenitors.

    “Notably, APC2 exhibited higher expression of fibrotic genes such as Fn1 and Loxl1 (Figure 3—figure supplement 1B), resembling ‘fibro-inflammatory progenitors’ (Hepler et al., 2018).”

    From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Hepler et al., 2018

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Cited by

Sorted by citations

Authors
Hepler, C., Shan, B., Zhang, Q., Henry, G. H., Shao, M., Vishvanath, L., Ghaben, A. L., Mobley, A. B., Strand, D., Hon, G. C., & Gupta, R. K.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Gupta, Rana K
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2018-09-28
Volume
7
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.39636
PMC
PMC6167054
OpenAlex
W2893679529
Cited by
346
References
7
Citations by year
2026: 32 · 2025: 38 · 2024: 48 · 2023: 50 · 2022: 53 · 2021: 52 · 2020: 48 · 2019: 24
FWCI
24.21
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (T32 GM008203, F31DK113696, DK098277, DK110497, DK104789)
  • American Heart Association (16POST26420136)
  • Cancer Prevention and Research Institute of Texas (RR140023)
  • National Institute of General Medical Sciences (DP2GM128203)
  • Welch Foundation (I-1926-20170325)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
visceral adipose tissue, adipose stromal cells, adipocyte precursors, adipogenesis, inflammation, fibrosis, NR4A nuclear receptors, perivascular cells, cell-cell interactions, white adipose tissue remodeling, metabolic dysfunction
MeSH terms
Aging, Animals, Antigens, Ly, Cell Differentiation, Cell Separation, Female, Fibrosis, Inflammation, Male, Mice, Inbred C57BL, Models, Biological, Phenotype, Stromal Cells, Sequence Analysis, RNA, Adipocytes, Receptor, Platelet-Derived Growth Factor beta, Gene Expression Profiling, Green Fluorescent Proteins, Intra-Abdominal Fat, Adipogenesis, Mice, Adipose Tissue, White, Single-Cell Analysis, Diet, High-Fat, Tetraspanin 29

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