生物
转录组
乳腺癌
癌症研究
癌相关成纤维细胞
生物标志物
癌症
核糖核酸
人口
计算生物学
肿瘤微环境
基因
基因表达
细胞
遗传学
医学
环境卫生
作者
Michael Bartoschek,Nikolay Oskolkov,Matteo Bocci,John Lövrot,Christer Larsson,Mikael N.E. Sommarin,Chris D. Madsen,David Lindgren,Gyula Pekár,Göran Karlsson,Markus Ringnér,Jonas Bergh,Åsa K. Björklund,Kristian Pietras
标识
DOI:10.1038/s41467-018-07582-3
摘要
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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