Project description:PROCR has been identified as a surface marker on cyclic mammary stem cells (MaSCs) in the basal layer of the mouse mammary gland. Due to their limited numbers, this population has not been clearly characterized. We performed single-cell multi-omics profiling of mammary epithelial cells enriched for PROCR+ cells. With an unprecedented number of PROCR+ cells, we found that this population is highly heterogeneous and identified the subpopulation most likely to resemble MaSCs. By integrating scRNA-seq and scATAC-seq data, we constructed the transcriptional regulatory network of mammary development and uncovered potential master regulators involved in lineage commitment. Motivated by the connection between PROCR's roles in normal mammary gland development and tumorigenesis, we further investigated this subpopulation in a cohort of breast cancer patients. As PROCR is a therapeutic target for a subset of TNBC, our study clarifies the nature of PROCR+ MaSCs and suggests the need for additional markers for patient stratification.
