Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38844451.
- Also identified by DOI 10.1038/s41467-024-48914-w and PMC identifier 11156882.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup>CD55<sup>low</sup> 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<sup>+</sup>CD55<sup>low</sup> 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.
Medical subject headings
- Single-Cell Analysis
- Diabetes Mellitus, Type 2
- Homeostasis
- Stem Cells
- Glucose
- Obesity