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Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling

Qishan Chen (), Ya Yu, Run Zhang, Qiaohang Zhao, Danqing Yu, Chun Feng, Jiaojiao Zhou, Meng Luo, Mei Yang, ShaSha Sun, Li Zhang () and Min Jin ()
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Qishan Chen: The Second Affiliated Hospital of Zhejiang University School of Medicine
Ya Yu: The Second Affiliated Hospital of Zhejiang University School of Medicine
Run Zhang: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Qiaohang Zhao: The Second Affiliated Hospital of Zhejiang University School of Medicine
Danqing Yu: The Second Affiliated Hospital of Zhejiang University School of Medicine
Chun Feng: The Second Affiliated Hospital of Zhejiang University School of Medicine
Jiaojiao Zhou: Zhejiang University School of Medicine
Meng Luo: Zhejiang University School of Medicine
Mei Yang: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
ShaSha Sun: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Li Zhang: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Min Jin: The Second Affiliated Hospital of Zhejiang University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract The global incidence of obesity-related metabolic disorders and their comorbidities continue to increase along with a demand for innovative therapeutic interventions. An in-depth understanding of de novo thermogenic adipogenesis is vital to harness the potential of these adipocytes. Here, we combine genetic lineage tracing and single-nucleus RNA sequencing to demonstrate that adult adipose-resident c-kit+ cells are previously unidentified brown adipocyte progenitor cells (APCs). c-kit+ APCs differentiate into brown adipocytes but not white adipocytes in adipose tissue homeostasis as well as in cold exposure-, high-fat diet (HFD)- and aging-induced adipose remodeling. More importantly, the vital role of c-kit+ APCs in the generation of brown adipocytes is indicated by decreased brown fat, impaired thermogenic capacity, and excessive fat accumulation in c-kit mutant mice of both genders. In conclusion, the present study demonstrates that adult c-kit+ APCs give rise to brown adipocytes which are responsible for fat homeostasis and remodeling. Thus, c-kit+ progenitors may be an innovative and crucial target for obesity and metabolic diseases.

Date: 2025
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DOI: 10.1038/s41467-025-60754-w

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