Trejo Christy L, Luna Gidsela, Dravis Christopher, Spike Benjamin T, Wahl Geoffrey M
Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, CA 92037 USA.
Huntsman Cancer Institute, University of Utah, Salt Lake City, 84103 UT USA.
NPJ Breast Cancer. 2017 Apr 24;3:16. doi: 10.1038/s41523-017-0018-6. eCollection 2017.
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.
寻找驱动乳腺发育的双能乳腺干细胞需要标记物，以便对其进行前瞻性分离。人们普遍认为，双能小鼠乳腺干细胞在胎儿发育后期数量丰富，但它们在成体中的存在存在激烈争论。在用于乳腺干细胞鉴定的标记物中，一些人认为Wnt共受体Lgr5对于成体乳腺干细胞活性的双能性和移植“既必要又充分”，但其他研究对此存在分歧。重要的是，Lgr5与胎儿乳腺干细胞双能性的相关性尚未得到研究。我们在此表明，由内源性Lgr5启动子驱动的荧光蛋白表达能够显著富集胎儿乳腺干细胞。我们使用谱系追踪来证明表达Lgr5的胚胎细胞具有双能性，而它们的成体对应细胞则局限于肌上皮。重要的是，我们的数据确凿地证明，Lgr5对于胎儿和成体乳腺干细胞活性以及乳腺肿瘤的发生发展都是可有可无的。
