Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages

To explore pre-cancer states during early malignancy, we evaluated tumor and normal cells in the MMTV-PyVT mouse model of luminal breast cancer using snRNAseq and snATACseq. B6.FVB-Tg(MMTV-PyVT) 634Mul/LellJ (Strain #:022974) female mice were purchased from the Jackson Laboratory. Mice were euthanized by carbon dioxide asphyxiation and five pairs of mouse mammary glands were collected at 12 weeks old. For each pair, the left mammary gland was flash frozen in liquid nitrogen, and the right glands were fixed in 10% neutral buffered formalin (Epredia, 5725) then embedded in paraffin. The 5 left mammary glands were pooled together for snRNA-Seq and snATAC-Seq sample preparation. The paraffin-embedded glands were used for H&E staining. All animal experiments were approved by the Washington University in Saint Louis Institutional Animal Care and Use Committee (IACUC) office.