Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes
Abstract Background The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods We conducted a sin...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04256-7 |
| _version_ | 1797778733622362112 |
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| author | Si-Qing Liu Ding-Yuan Chen Bei Li Zhi-Jie Gao Hong-Fang Feng Xin Yu Zhou Liu Yuan Wang Wen-Ge Li Si Sun Sheng-Rong Sun Qi Wu |
| author_facet | Si-Qing Liu Ding-Yuan Chen Bei Li Zhi-Jie Gao Hong-Fang Feng Xin Yu Zhou Liu Yuan Wang Wen-Ge Li Si Sun Sheng-Rong Sun Qi Wu |
| author_sort | Si-Qing Liu |
| collection | DOAJ |
| description | Abstract Background The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods We conducted a single-cell RNA sequencing analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. Results We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipocytes in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. Conclusion Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future. |
| first_indexed | 2024-03-12T23:21:45Z |
| format | Article |
| id | doaj.art-ddc17bc4f4074fed9e1e0361ffef075f |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-12T23:21:45Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-ddc17bc4f4074fed9e1e0361ffef075f2023-07-16T11:26:34ZengBMCJournal of Translational Medicine1479-58762023-07-0121112010.1186/s12967-023-04256-7Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypesSi-Qing Liu0Ding-Yuan Chen1Bei Li2Zhi-Jie Gao3Hong-Fang Feng4Xin Yu5Zhou Liu6Yuan Wang7Wen-Ge Li8Si Sun9Sheng-Rong Sun10Qi Wu11Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan UniversityDepartment of Breast and Thyroid Surgery, Renmin Hospital of Wuhan UniversityDepartment of Pathology, Renmin Hospital of Wuhan UniversityDepartment of Breast and Thyroid Surgery, Renmin Hospital of Wuhan UniversityDepartment of Breast and Thyroid Surgery, Huangshi Central Hospital, Hubei Polytechnic UniversityDepartment of Breast and Thyroid Surgery, Renmin Hospital of Wuhan UniversityDepartment of Breast and Thyroid Surgery, Renmin Hospital of Wuhan UniversityDepartment of Breast and Thyroid Surgery, Renmin Hospital of Wuhan UniversityDepartment of Oncology, Shanghai Artemed HospitalDepartment of Clinical Laboratory, Renmin Hospital of Wuhan UniversityDepartment of Breast and Thyroid Surgery, Renmin Hospital of Wuhan UniversityTongji University Cancer Center, Shanghai Tenth People’s Hospital, Tongji University School of MedicineAbstract Background The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods We conducted a single-cell RNA sequencing analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. Results We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipocytes in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. Conclusion Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future.https://doi.org/10.1186/s12967-023-04256-7Tumor-adipose microenvironmentSingle-cell RNA sequencingCancer-associated adipocytesAdiponectin receptor |
| spellingShingle | Si-Qing Liu Ding-Yuan Chen Bei Li Zhi-Jie Gao Hong-Fang Feng Xin Yu Zhou Liu Yuan Wang Wen-Ge Li Si Sun Sheng-Rong Sun Qi Wu Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes Journal of Translational Medicine Tumor-adipose microenvironment Single-cell RNA sequencing Cancer-associated adipocytes Adiponectin receptor |
| title | Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes |
| title_full | Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes |
| title_fullStr | Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes |
| title_full_unstemmed | Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes |
| title_short | Single-cell analysis of white adipose tissue reveals the tumor-promoting adipocyte subtypes |
| title_sort | single cell analysis of white adipose tissue reveals the tumor promoting adipocyte subtypes |
| topic | Tumor-adipose microenvironment Single-cell RNA sequencing Cancer-associated adipocytes Adiponectin receptor |
| url | https://doi.org/10.1186/s12967-023-04256-7 |
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