Abstract Epigenetic regulation is essential for mammary gland development, yet the specific chromatin remodelers that govern mammary epithelial cell fate remain poorly defined. Mutations in SWI/SNF chromatin remodeling complex subunits occur in more than 20% of human cancers, with ARID1A being the most frequently altered. In breast cancer, ARID1A loss of function mutations are enriched in metastatic estrogen receptor-positive (ER+) disease and associated with endocrine therapy resistance. To define the developmental role of Arid1a in vivo, we generated mice with mammary epithelium specific Arid1a deletion. These animals displayed disrupted ductal branching and aberrant terminal end bud formation. Mammary organoids derived from Arid1a deficient tissue further revealed abnormal cystic morphology and impaired differentiation. To dissect the molecular consequences of Arid1a loss, we performed single cell multiomic profiling that combine single nucleus RNA and chromatin accessibility sequencing from the same cells, together with H3K27ac and BRG1 CUT Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3219.
Ladewig et al. (Fri,) studied this question.