ICAM-1 identifies preadipocytes and restricts white adipogenesis by adhering immune cells
Adipose stem cell hierarchy was delineated by scRNA-seq analysis, revealing that ICAM-1, a glycoprotein that mediates cell-cell interaction, is a preadipocyte marker. However, the cellular and molecular mechanisms of how ICAM-1<sup>+</sup> preadipocytes contribute to adipose tissue homeostasis in vivo remain unclear. To address this, Icam1<sup>+/CreERT2</sup> mice were generated, and it was demonstrated that ICAM-1-expressing progenitors actively participated in developing and remodeling white adipose tissue. Under a high-fat diet, both proliferation and adipogenic differentiation of ICAM-1<sup>+</sup> preadipocytes increased significantly. Interestingly, ICAM-1 plays a critical role in maintaining the interaction between preadipocytes and immune cells, acting as a checkpoint on white adipogenesis. Mice lacking ICAM-1 specifically in stromal cells exhibited worsened hyperplastic obesity, showing heightened fatty acid synthesis and lipid storage in adipose tissue, and the related insulin resistance. In human adipose tissue, ICAM-1 also marked committed preadipocytes and mediated adhesion between preadipocytes and immune cells. Thus, our study shows that ICAM-1 marks preadipocytes and curbs adipogenesis by facilitating adhesion between preadipocytes and immune cells.
Authors
- Jiayin Ye (ORCID: https://orcid.org/0000-0002-4695-8287)
- Arnold B. Rabson (ORCID: https://orcid.org/0000-0001-5651-2521)
- Yueqing Xue (ORCID: https://orcid.org/0000-0003-0762-912X)
- Keli Liu (ORCID: https://orcid.org/0000-0001-8008-2162)
- Lydia Sorokin (ORCID: https://orcid.org/0000-0001-7704-7921)
- Gerry Melino (ORCID: https://orcid.org/0000-0001-9428-5972)
- Fei Hua (ORCID: https://orcid.org/0000-0001-7452-6871)
- Hui Ma (ORCID: https://orcid.org/0000-0003-2942-597X)
- Yufang Shi (ORCID: https://orcid.org/0000-0001-8964-319X)
- Changshun Shao (ORCID: https://orcid.org/0000-0003-2618-9342)
- Qing Li (ORCID: https://orcid.org/0000-0003-1990-5857)
- Qian Yang (ORCID: https://orcid.org/0000-0003-2304-9408)
- Jianchang Cao
- Chunxing Zheng (ORCID: https://orcid.org/0000-0002-8668-0873)
- Ying Wang (ORCID: https://orcid.org/0000-0002-2571-9367)
- Cheng Chen (ORCID: https://orcid.org/0009-0001-6411-0394)
Institutions
- University of Rome Tor Vergata (IT)
- University of Münster (DE)
- Fudan University (CN)
- Johnson University (US)
- Soochow University (CN)
- Shanghai Institute of Nutrition and Health (CN)
- Second Affiliated Hospital of Soochow University (CN)
- Zhongshan Hospital (CN)
- Jiangsu University of Technology (CN)
- First Affiliated Hospital of Soochow University (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Cell Death and Differentiation
- Published
- 2025-08-14
- DOI
- https://doi.org/10.1038/s41418-025-01551-2
- Citations
- 1
- Primary Topic
- Adipokines, Inflammation, and Metabolic Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.35