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

Summary: Aiming to unravel the top of the mammary epithelial cell hierarchy, a subset of the CD49fhighCD24med mammary repopulating units (MRUs) was identified by flow cytometry, expressing high levels of CD200 and its receptor CD200R1. These MRUCD200/CD200R1 repopulated a larger area of de-epithelized mammary fat pads than the rest of the MRUs, termed MRUnot CD200/CD200R1. MRUCD200/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 MRUnot 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 MRUCD200/CD200R1 via MRUnot 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. : Barash and colleagues show that high expression levels of the immunoglobulin proteins CD200 and CD200R1 distinguish stem from progenitor cells with unique characteristics within the mammary repopulating units. This finding enables enrichment of the stem cell population. It contributes to elucidating the composition at the top of the mammary cell hierarchy that enables cyclic regeneration periods between lactations. Keywords: mammary gland, stem cells, CD200, CD200R