CD81 通过 FAK 信号控制米色脂肪祖细胞的生长和能量平衡。
CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling.
机构信息
UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA; Beth Israel Deaconess Medical Center, Division of Endocrinology, Diabetes & Metabolism, Harvard Medical School, Boston, MA, USA.
UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, New York, NY, USA.
出版信息
Cell. 2020 Aug 6;182(3):563-577.e20. doi: 10.1016/j.cell.2020.06.021. Epub 2020 Jul 1.
Adipose tissues dynamically remodel their cellular composition in response to external cues by stimulating beige adipocyte biogenesis; however, the developmental origin and pathways regulating this process remain insufficiently understood owing to adipose tissue heterogeneity. Here, we employed single-cell RNA-seq and identified a unique subset of adipocyte progenitor cells (APCs) that possessed the cell-intrinsic plasticity to give rise to beige fat. This beige APC population is proliferative and marked by cell-surface proteins, including PDGFRα, Sca1, and CD81. Notably, CD81 is not only a beige APC marker but also required for de novo beige fat biogenesis following cold exposure. CD81 forms a complex with αV/β1 and αV/β5 integrins and mediates the activation of integrin-FAK signaling in response to irisin. Importantly, CD81 loss causes diet-induced obesity, insulin resistance, and adipose tissue inflammation. These results suggest that CD81 functions as a key sensor of external inputs and controls beige APC proliferation and whole-body energy homeostasis.
脂肪组织通过刺激米色脂肪细胞生成来动态重塑其细胞组成以响应外部信号；然而，由于脂肪组织异质性，米色脂肪细胞生成的发育起源和调控途径仍了解不足。在这里，我们采用单细胞 RNA 测序技术，鉴定出一种独特的脂肪细胞祖细胞（APC）亚群，其具有内在的可塑性，能够产生米色脂肪。这种米色 APC 群体具有增殖能力，其表面标志物包括 PDGFRα、Sca1 和 CD81。值得注意的是，CD81 不仅是米色 APC 的标志物，而且在冷暴露后新生成米色脂肪中也需要 CD81。CD81 与 αV/β1 和 αV/β5 整联蛋白形成复合物，并介导整合素-FAK 信号的激活以响应鸢尾素。重要的是，CD81 的缺失会导致饮食诱导的肥胖、胰岛素抵抗和脂肪组织炎症。这些结果表明，CD81 作为外部输入的关键传感器，控制米色 APC 的增殖和全身能量稳态。
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