Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Single-Cell Analysis*/methods ; Diabetes Mellitus, Type 2*/metabolism ; Homeostasis* ; Stem Cells*/metabolism ; Glucose*/metabolism ; Obesity*/metabolism ; Obesity*/pathology; Humans ; Animals ; Male ; Mice ; Adipocytes/metabolism ; Intra-Abdominal Fat/metabolism ; Intra-Abdominal Fat/cytology ; Adipose Tissue/metabolism ; Adipose Tissue/cytology ; Mice, Inbred C57BL ; Lipolysis ; Female ; Middle Aged
    • Abstract:
      Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9 + CD55 low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9 + CD55 low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.
      (© 2024. The Author(s).)
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    • Accession Number:
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20240606 Date Completed: 20240606 Latest Revision: 20240609
    • Publication Date:
      20240609
    • Accession Number:
      PMC11156882
    • Accession Number:
      10.1038/s41467-024-48914-w
    • Accession Number:
      38844451