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CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling.

  • Author(s): Oguri, Yasuo
  • Shinoda, Kosaku
  • Kim, Hyeonwoo
  • Alba, Diana L
  • Bolus, W Reid
  • Wang, Qiang
  • Brown, Zachary
  • Pradhan, Rachana N
  • Tajima, Kazuki
  • Yoneshiro, Takeshi
  • Ikeda, Kenji
  • Chen, Yong
  • Cheang, Rachel T
  • Tsujino, Kazuyuki
  • Kim, Caroline R
  • Greiner, Vanille Juliette
  • Datta, Ritwik
  • Yang, Christopher D
  • Atabai, Kamran
  • McManus, Michael T
  • Koliwad, Suneil K
  • Spiegelman, Bruce M
  • Kajimura, Shingo
  • et al.
Abstract

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.

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