<p>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, <i>Icam1</i><sup><i>+/CreERT2</i></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.</p>

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ICAM-1 identifies preadipocytes and restricts white adipogenesis by adhering immune cells

  • Chunxing Zheng,
  • Jiayin Ye,
  • Qian Yang,
  • Keli Liu,
  • Cheng Chen,
  • Jianchang Cao,
  • Qing Li,
  • Yueqing Xue,
  • Hui Ma,
  • Arnold B. Rabson,
  • Changshun Shao,
  • Fei Hua,
  • Lydia Sorokin,
  • Gerry Melino,
  • Yufang Shi,
  • Ying Wang

摘要

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+ preadipocytes contribute to adipose tissue homeostasis in vivo remain unclear. To address this, Icam1+/CreERT2 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+ 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.