期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-07582-3
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资金
- European Research Council (the TUMORGAN project) [309322]
- Swedish Research Council
- Swedish Cancer Society
- STARGET consortium (Swedish Research Council Linnaeus network)
- Biltema foundation
- BioCARE
- SciLifeLab WABI
- Sydsvenska Brostcancergruppen
- Fru Berta Kamprads stiftelse
- Region Skane ALF
- Lund University
- European Research Council (ERC) [309322] Funding Source: European Research Council (ERC)
Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium. Gene profiles for each CAF subtype correlate to distinctive functional programs and hold independent prognostic capability in clinical cohorts by association to metastatic disease. In conclusion, the improved resolution of the widely defined CAF population opens the possibility for biomarker-driven development of drugs for precision targeting of CAFs.
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