Abstract
The search for the bipotent mammary stem cells that drive mammary development requires markers to enable their prospective isolation. There is general agreement that bipotent mouse mammary stem cells are abundant in late fetal development, but their existence in the adult is vigorously debated. Among markers useful for mammary stem cell identification, the Wnt co-receptor Lgr5 has been suggested by some to be both “necessary and sufficient” for bipotency and transplantation of adult mammary stem cell activity, though other studies disagree. Importantly, the relevance of Lgr5 to the bipotency of fetal mammary stem cells has not been studied. We show here that expression of a fluorescent protein driven by the endogenous Lgr5 promoter enables significant fetal mammary stem cell enrichment. We used lineage tracing to demonstrate embryonic cells expressing Lgr5 are bipotent, while their adult counterparts are myoepithelial restricted. Importantly, our data conclusively demonstrate that Lgr5 is dispensable for both fetal and adult mammary stem cell activity and for the development of mammary tumors.
Highlights
The identification of reliable markers useful for prospective identification and isolation of mammary stem cells (MaSCs) is critical for gaining a better understanding of mammary development and breast cancers that co-opt developmental and stem cell mechanisms
In order to understand the role of Lgr[5] as a marker for MaSC activity, we first profiled the dynamics of its expression at time points in development at which quantitation of stem cell activity showed dramatic differences.[13]
We performed immunofluorescent staining using an antibody against GFP in whole mount mammary glands from embryonic stages 15 (E15), 17 (E17), and adult virgin mice
Summary
The identification of reliable markers useful for prospective identification and isolation of mammary stem cells (MaSCs) is critical for gaining a better understanding of mammary development and breast cancers that co-opt developmental and stem cell mechanisms. In this regard, markers with functional relevance would be extremely valuable, as they might serve as therapeutic targets in specific cells or molecular processes. Wnt signaling plays a functional role in epithelial stem cell biology, and has been shown to be critical for early stages of mammary development and breast cancer.[1,2,3,4] Wnt signaling has been suggested to play a role in MaSCs.[5,6,7,8] Lgr[5], a G-proteincoupled receptor involved in canonical Wnt signaling, was proposed as a marker for adult MaSCs, but other reports do not support this conclusion.[9,10,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
