Department of Developmental Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Cell Stem Cell. 2012 Sep 7;11(3):387-400. doi: 10.1016/j.stem.2012.05.023. Epub 2012 Aug 2.
The mammary epithelium undergoes extensive growth and remodeling during pregnancy, suggesting a role for stem cells. Yet their origin, identity, and behavior in the intact tissue remain unknown. Using an Axin2(CreERT2) allele, we labeled and traced Wnt/β-catenin-responsive cells throughout mammary gland development. This reveals a switch in Wnt/β-catenin signaling around birth and shows that, depending on the developmental stage, Axin2(+) cells contribute differently to basal and luminal epithelial cell lineages of the mammary epithelium. Moreover, an important difference exists between the developmental potential tested in transplantation assays and that displayed by the same cell population in situ. Finally, Axin2(+) cells in the adult build alveolar structures during multiple pregnancies, demonstrating the existence of a Wnt/β-catenin-responsive adult stem cell. Our study uncovers dynamic changes in Wnt/β-catenin signaling in the mammary epithelium and offers insights into the developmental fate of mammary gland stem and progenitor cells.
乳腺上皮在怀孕期间经历广泛的生长和重塑，这表明干细胞在其中发挥作用。然而，其在完整组织中的起源、身份和行为仍不清楚。我们利用 Axin2(CreERT2) 等位基因标记和追踪了乳腺发育过程中对 Wnt/β-catenin 有反应的细胞。这揭示了出生前后 Wnt/β-catenin 信号的转换，并表明，根据发育阶段的不同，Axin2(+)细胞对乳腺上皮的基底和腔上皮细胞谱系的贡献不同。此外，在移植实验中测试的发育潜力与同一细胞群在原位显示的发育潜力之间存在重要差异。最后，在多次妊娠期间，成年 Axin2(+)细胞构建了肺泡结构，证明了 Wnt/β-catenin 反应性成体干细胞的存在。我们的研究揭示了乳腺上皮中 Wnt/β-catenin 信号的动态变化，并为乳腺干细胞和祖细胞的发育命运提供了新的见解。
