Chen Qishan, Yu Ya, Zhang Run, Zhao Qiaohang, Yu Danqing, Feng Chun, Zhou Jiaojiao, Luo Meng, Yang Mei, Sun ShaSha, Zhang Li, Jin Min
Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Institute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Nat Commun. 2025 Jul 1;16(1):5883. doi: 10.1038/s41467-025-60754-w.
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.
肥胖相关代谢紊乱及其合并症的全球发病率持续上升，同时对创新治疗干预措施的需求也在增加。深入了解新生脂肪生成对于挖掘这些脂肪细胞的潜力至关重要。在这里，我们结合基因谱系追踪和单核RNA测序，证明成年脂肪组织驻留的c-kit细胞是先前未被识别的棕色脂肪细胞祖细胞（APC）。在脂肪组织稳态以及冷暴露、高脂饮食（HFD）和衰老诱导的脂肪重塑过程中，c-kit APC分化为棕色脂肪细胞而非白色脂肪细胞。更重要的是，在两性的c-kit突变小鼠中，棕色脂肪减少、产热能力受损和脂肪过度积累表明了c-kit APC在棕色脂肪细胞生成中的重要作用。总之，本研究表明成年c-kit APC产生负责脂肪稳态和重塑的棕色脂肪细胞。因此，c-kit祖细胞可能是肥胖和代谢疾病的一个创新且关键的靶点。
