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

Author

Listed:
  • Hongdong Wang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Yanhua Du

    (Shanghai Jiao Tong University School of Medicine)

  • Shanshan Huang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Xitai Sun

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Youqiong Ye

    (Shanghai Jiao Tong University School of Medicine)

  • Haixiang Sun

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Xuehui Chu

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Xiaodong Shan

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Yue Yuan

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Lei Shen

    (Shanghai Jiao Tong University School of Medicine)

  • Yan Bi

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

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+CD55low 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+CD55low 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.

Suggested Citation

  • Hongdong Wang & Yanhua Du & Shanshan Huang & Xitai Sun & Youqiong Ye & Haixiang Sun & Xuehui Chu & Xiaodong Shan & Yue Yuan & Lei Shen & Yan Bi, 2024. "Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48914-w
    DOI: 10.1038/s41467-024-48914-w
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