Meflin/ISLR is a marker of adipose stem and progenitor cells in mice and humans that suppresses white adipose tissue remodeling and fibrosis

Genes Cells. 2024 Oct;29(10):902-920. doi: 10.1111/gtc.13154. Epub 2024 Aug 13.

Abstract

Identifying specific markers of adipose stem and progenitor cells (ASPCs) in vivo is crucial for understanding the biology of white adipose tissues (WAT). PDGFRα-positive perivascular stromal cells represent the best candidates for ASPCs. This cell lineage differentiates into myofibroblasts that contribute to the impairment of WAT function. However, ASPC marker protein(s) that are functionally crucial for maintaining WAT homeostasis are unknown. We previously identified Meflin as a marker of mesenchymal stem cells (MSCs) in bone marrow and tissue-resident perivascular fibroblasts in various tissues. We also demonstrated that Meflin maintains the undifferentiated status of MSCs/fibroblasts. Here, we show that Meflin is expressed in WAT ASPCs. A lineage-tracing experiment showed that Meflin+ ASPCs proliferate in the WAT of obese mice induced by a high-fat diet (HFD), while some of them differentiate into myofibroblasts or mature adipocytes. Meflin knockout mice fed an HFD exhibited a significant fibrotic response as well as increases in adipocyte cell size and the number of crown-like structures in WAT, accompanied by impaired glucose tolerance. These data suggested that Meflin expressed by ASPCs may have a role in reducing disease progression associated with WAT dysfunction.

Keywords: Islr; Meflin; adipose stem and progenitor cells; adipose stem cells; fibrosis; glucose tolerance; immunoglobulin superfamily containing leucine‐rich repeat; mesenchymal stem cell; metabolic syndrome.

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue, White* / metabolism
  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Diet, High-Fat / adverse effects
  • Fibrosis* / metabolism
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Stem Cells / metabolism

Substances

  • Biomarkers