Pre-neoplastic stromal cells drive BRCA1-mediated breast tumorigenesis

Women with germline mtuation in BRCA1 have increased risk for developing hereditary breast cancer. The role of the epitheilum-assocaited niche during BRCA1-driven tumor intiation remains unclear. Here, we show that the pre-malignant stromal niche promotes epithelial prolifeation and BRCA1-driven cancer intiation in trans. Using single-cell RNA seq analysis of human pre-neoplastic BRCA1 and control breast tissue, we show that stromal cells provide numerous pro-proliferative paracrine signals inducing epithelial proliferation. Overall design: Library generation for four 10x genomics v1 chemistry, and twenty-four 10x genomics v2 chemistry was performed following the Chromim Singel Cell 3' Reagents Kits v2 User Guide: CFG00052 Rev B. Libraries were sequenced on the Illumina NovaSeq6000 platform targeting approximately 50,000 reads per cell.