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

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

doi:10.1016/j.cell.2020.06.021

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

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

Medicine

Research output: Contribution to journal › Article › peer-review

148 Scopus citations

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.

Original language	English (US)
Pages (from-to)	563-577.e20
Journal	Cell
Volume	182
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2020.06.021
State	Published - Aug 6 2020

Keywords

adipocyte progenitors
adipogenesis
beige fat
brown fat
diabetes
metabolic adaptation
metabolic disease
metabolism
obesity
tissue remodeling

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2020.06.021

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Oguri, Y., Shinoda, K., Kim, H., Alba, D. L., Bolus, W. R., Wang, Q., Brown, Z., Pradhan, R. N., Tajima, K., Yoneshiro, T., Ikeda, K., Chen, Y., Cheang, R. T., Tsujino, K., Kim, C. R., Greiner, V. J., Datta, R., Yang, C. D., Atabai, K., ... Kajimura, S. (2020). CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling. Cell, 182(3), 563-577.e20. https://doi.org/10.1016/j.cell.2020.06.021

Oguri, Y, Shinoda, K, Kim, H, Alba, DL, Bolus, WR, Wang, Q, Brown, Z, Pradhan, RN, Tajima, K, Yoneshiro, T, Ikeda, K, Chen, Y, Cheang, RT, Tsujino, K, Kim, CR, Greiner, VJ, Datta, R, Yang, CD, Atabai, K, McManus, MT, Koliwad, SK, Spiegelman, BM & Kajimura, S 2020, 'CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling', Cell, vol. 182, no. 3, pp. 563-577.e20. https://doi.org/10.1016/j.cell.2020.06.021

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title = "CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling",

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.",

keywords = "adipocyte progenitors, adipogenesis, beige fat, brown fat, diabetes, metabolic adaptation, metabolic disease, metabolism, obesity, tissue remodeling",

author = "Yasuo Oguri and Kosaku Shinoda and Hyeonwoo Kim and Alba, {Diana L.} and Bolus, {W. Reid} and Qiang Wang and Zachary Brown and Pradhan, {Rachana N.} and Kazuki Tajima and Takeshi Yoneshiro and Kenji Ikeda and Yong Chen and Cheang, {Rachel T.} and Kazuyuki Tsujino and Kim, {Caroline R.} and Greiner, {Vanille Juliette} and Ritwik Datta and Yang, {Christopher D.} and Kamran Atabai and McManus, {Michael T.} and Koliwad, {Suneil K.} and Spiegelman, {Bruce M.} and Shingo Kajimura",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = aug,

day = "6",

doi = "10.1016/j.cell.2020.06.021",

language = "English (US)",

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AU - Oguri, Yasuo

AU - Shinoda, Kosaku

AU - Kim, Hyeonwoo

AU - Alba, Diana L.

AU - Bolus, W. Reid

AU - Wang, Qiang

AU - Brown, Zachary

AU - Pradhan, Rachana N.

AU - Tajima, Kazuki

AU - Yoneshiro, Takeshi

AU - Ikeda, Kenji

AU - Chen, Yong

AU - Cheang, Rachel T.

AU - Tsujino, Kazuyuki

AU - Kim, Caroline R.

AU - Greiner, Vanille Juliette

AU - Datta, Ritwik

AU - Yang, Christopher D.

AU - Atabai, Kamran

AU - McManus, Michael T.

AU - Koliwad, Suneil K.

AU - Spiegelman, Bruce M.

AU - Kajimura, Shingo

PY - 2020/8/6

Y1 - 2020/8/6

N2 - 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.

AB - 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.

KW - adipocyte progenitors

KW - adipogenesis

KW - beige fat

KW - brown fat

KW - diabetes

KW - metabolic adaptation

KW - metabolic disease

KW - metabolism

KW - obesity

KW - tissue remodeling

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AN - SCOPUS:85087450069

SN - 0092-8674

VL - 182

SP - 563-577.e20

JO - Cell

JF - Cell

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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