Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2018 Jun 29;360(6396). doi: 10.1126/science.aan4153. Epub 2018 May 17.
The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. We show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche in mouse models. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feedback loop that promotes the function of Dll1-expressing MaSCs. Together, these findings reveal functionally important cross-talk between MaSCs and their macrophageal niche through Dll1-mediated Notch signaling.
干细胞龛是一个专门的环境，决定了干细胞在发育和体内平衡过程中的功能。我们表明，Notch 通路配体 Dll1 在乳腺干细胞 (MaSCs) 中富集，并在小鼠模型中与周围龛位的基质巨噬细胞进行关键相互作用。条件性删除 Dll1 会减少 MaSCs 的数量并损害乳腺的导管形态发生。此外，MaSC 表达的 Dll1 激活了基质巨噬细胞中的 Notch 信号通路，增加了它们表达 Wnt 家族配体，如 Wnt3、Wnt10A 和 Wnt16，从而启动一个反馈回路，促进表达 Dll1 的 MaSCs 的功能。总之，这些发现揭示了 MaSCs 和它们的巨噬细胞龛之间通过 Dll1 介导的 Notch 信号进行功能上重要的交叉对话。
