DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation.

ABSTRACT: Understanding epithelial stem cell differentiation and morphogenesis during breast tissue development is essential, as disruption in these processes underlie breast cancer formation. We used a next-generation single-cell-derived organoid model to investigate how individual stem cells give rise to complex tissue. We show that discoidin domain receptor 1 (DDR1) inhibition traps cells in a bipotent state, blocking alveolar morphogenesis and luminal cell expansion, which is necessary for complex epithelium formation. Disrupting RUNX1 function produced nearly identical phenotypes, underscoring its critical role downstream of DDR1. Mechanistically, DDR1 affects the interaction and expression of RUNX1 and its cofactor core binding factor beta (CBFβ), thereby regulating its activity. Mutational an

SUBMITTER: Trepicchio C 

PROVIDER: S-EPMC12365826 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature