High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell Populations within Mammary Repopulating Units

Aiming to unravel the top of the mammary epithelial cell hierarchy, a subset of the CD49f(high)CD24(med) mammary repopulating units (MRUs) was identified by flow cytometry, expressing high levels of CD200 and its receptor CD200R1. These MRU(CD200/CD200R1) repopulated a larger area of de-epithelized mammary fat pads than the rest of the MRUs, termed MRU(not CD200/CD200R1). MRU(CD200/CD200R1) maintained a much lower number of divergently defined, highly expressed genes and pathways that support better cell growth, development, differentiation, and progenitor activity than their MRU(not CD200/CD200R1) counterparts. A defined profile of hierarchically associated genes supporting a single-lineage hypothesis was confirmed by in vitro mammosphere analysis that assembled 114 genes with decreased expression from MRU(CD200/CD200R1) via MRU(not CD200/CD200R1) toward CD200(+)CD200R1(−) and CD200R1(+)CD200(−) cells. About 40% of these genes were shared by a previously published database of upregulated genes in mammary/breast stem cells and may represent the core genes involved in mammary stemness.