Epigenetic and Transcriptomic Profiling of Mammary Gland Development and Tumor Models Disclose Regulators of Cell State Plasticity

摘要: Cell state reprogramming during tumor progression complicates accurate diagnosis, compromises therapeutic effectiveness, and fuels metastatic dissemination. We used chromatin accessibility assays transcriptional profiling mammary development as an agnostic approach to identify factors that mediate cancer cell interconversions. show fetal adult basal cells share epigenetic features consistent with multi-lineage differentiation potential. find DNA-binding motifs for SOX transcription are enriched in is accessible stem/progenitor inaccessible differentiated cells. In both mouse human tumors, SOX10 expression correlates identity, dedifferentiation, invasive characteristics. Strikingly, we demonstrate binds genes regulate neural crest SOX10-positive exhibit features.