间质细胞
生物
受体酪氨酸激酶
细胞外基质
细胞生物学
癌症研究
FGF10型
成纤维细胞
成纤维细胞生长因子
形态发生
肌成纤维细胞
信号转导
细胞培养
病理
受体
遗传学
基因
医学
纤维化
作者
Jiyong Li,Ruijuan Ma,Xuebing Wang,Yunzhe Lu,Jing Chen,Feng Dai,Jiahao Zhou,Kun Xia,Ophir D. Klein,Hao Xie,Pengfei Lu
标识
DOI:10.1038/s41419-024-06637-2
摘要
Abstract Stromal fibroblasts are a major stem cell niche component essential for organ formation and cancer development. Fibroblast heterogeneity, as revealed by recent advances in single-cell techniques, has raised important questions about the origin, differentiation, and function of fibroblast subtypes. In this study, we show in mammary stromal fibroblasts that loss of the receptor tyrosine kinase (RTK) negative feedback regulators encoded by Spry1 , Spry2 , and Spry4 causes upregulation of signaling in multiple RTK pathways and increased extracellular matrix remodeling, resulting in accelerated epithelial branching. Single-cell transcriptomic analysis demonstrated that increased production of FGF10 due to Sprouty ( Spry ) loss results from expansion of a functionally distinct subgroup of fibroblasts with the most potent branching-promoting ability. Compared to their three independent lineage precursors, fibroblasts in this subgroup are “activated,” as they are located immediately adjacent to the epithelium that is actively undergoing branching and invasion. Spry genes are downregulated, and activated fibroblasts are expanded, in all three of the major human breast cancer subtypes. Together, our data highlight the regulation of a functional subtype of mammary fibroblasts by Spry genes and their essential role in epithelial morphogenesis and cancer development.
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