Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143-0452, USA.
Cell Rep. 2013 Jan 31;3(1):70-8. doi: 10.1016/j.celrep.2012.12.017. Epub 2013 Jan 24.
Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5(+)) mammary epithelial cells (MECs). We found that Lgr5(+) cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs), are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5(+) cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis.
乳腺上皮干细胞对于乳腺在出生后各个阶段的组织扩张和重塑至关重要。基底乳腺上皮细胞富含对 Wnt 有反应的细胞，并且可以在移植到小鼠中后重新构成清除的乳腺脂肪垫。Lgr5 是 Wnt 调节的靶基因，被鉴定为小肠、结肠、胃和毛囊以及肾单位中的主要干细胞标记物。在这里，我们证明了表达 Lgr5（Lgr5(+)）的乳腺上皮细胞（MEC）的罕见群体具有出色的再生潜力。我们发现 Lgr5(+)细胞位于基底细胞群中，在再生功能性乳腺（MG）方面优于其他基底细胞，从单个细胞重建 MG 的效率非常高，并且在连续移植中具有再生能力。从移植的 MEC 或青春期 MG 中 Lgr5(+)细胞的功能丧失和耗竭实验表明，这些细胞不仅是充分的，而且对于出生后乳腺器官发生也是必需的。
