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

Abstract

Aiming to unravel the top of the mammary epithelial cell hierarchy, a subset of the CD49f^highCD24^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.

Keywords: CD200; CD200R1; mammary gland; stem cells.