2. Academic Validation
  3. Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling

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

  • Nat Commun. 2025 Jul 1;16(1):5883. doi: 10.1038/s41467-025-60754-w.
Qishan Chen # 1 2,  Ya Yu # 3,  Run Zhang # 4,  Qiaohang Zhao 3,  Danqing Yu 3,  Chun Feng 3,  Jiaojiao Zhou 5,  Meng Luo 5,  Mei Yang 4,  ShaSha Sun 4,  Li Zhang 6,  Min Jin 7
Affiliations

Affiliations

  • 1 Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. lastufo@hotmail.com.
  • 2 Institute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. lastufo@hotmail.com.
  • 3 Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Institute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 5 The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of Medicine, Hangzhou, China.
  • 6 Institute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. li.zhang@shsmu.edu.cn.
  • 7 Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. min_jin@zju.edu.cn.
  • # Contributed equally.
PMID: 40593548 DOI: 10.1038/s41467-025-60754-w
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.

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