Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling
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, w...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60754-w |
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| _version_ | 1849334595339681792 |
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| author | Qishan Chen Ya Yu Run Zhang Qiaohang Zhao Danqing Yu Chun Feng Jiaojiao Zhou Meng Luo Mei Yang ShaSha Sun Li Zhang Min Jin |
| author_facet | Qishan Chen Ya Yu Run Zhang Qiaohang Zhao Danqing Yu Chun Feng Jiaojiao Zhou Meng Luo Mei Yang ShaSha Sun Li Zhang Min Jin |
| author_sort | Qishan Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-273301dee2ac4630b8e9778c1fc8b64f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-273301dee2ac4630b8e9778c1fc8b64f2025-08-20T03:45:31ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-60754-wCommitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodelingQishan Chen0Ya Yu1Run Zhang2Qiaohang Zhao3Danqing Yu4Chun Feng5Jiaojiao Zhou6Meng Luo7Mei Yang8ShaSha Sun9Li Zhang10Min Jin11Department of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineInstitute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineDepartment of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineThe Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of MedicineThe Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Zhejiang University School of MedicineInstitute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineInstitute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineInstitute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineDepartment of Reproductive Medicine, The Second Affiliated Hospital of Zhejiang University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-60754-w |
| spellingShingle | Qishan Chen Ya Yu Run Zhang Qiaohang Zhao Danqing Yu Chun Feng Jiaojiao Zhou Meng Luo Mei Yang ShaSha Sun Li Zhang Min Jin Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling Nature Communications |
| title | Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling |
| title_full | Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling |
| title_fullStr | Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling |
| title_full_unstemmed | Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling |
| title_short | Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling |
| title_sort | commitment of adipose resident c kit progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling |
| url | https://doi.org/10.1038/s41467-025-60754-w |
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