A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells.

ABSTRACT: Germline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations. Here, we report that monoallelic Brca2^mut/WT mammary organoids subjected to replication stress activate a transcriptional response that selectively expands Brca2^mut/WT luminal cells lacking hormone receptor expression (HR-). While CyTOF analyses reveal comparable epithelial compositions among wildtype and Brca2^mut/WT mammary glands, Brca2^mut/WT HR- luminal cells exhibit greater organoid formation and preferentially survive and expand under replication stress. ScRNA-seq analysis corroborates the expansion of HR- luminal cells which express elevated transcript levels of Tetraspanin-8 (

SUBMITTER: Najafabadi MG 

PROVIDER: S-EPMC10457340 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature