Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche.

TitleNotch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche.
Publication TypeJournal Article
Year of Publication2018
AuthorsChakrabarti, R, Celià-Terrassa, T, Kumar, S, Hang, X, Wei, Y, Choudhury, A, Hwang, J, Peng, J, Nixon, B, Grady, JJ, DeCoste, C, Gao, J, van Es, JH, Li, MO, Aifantis, I, Clevers, H, Kang, Y
JournalScience
Date Published2018 May 17
ISSN1095-9203
Abstract

The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. Here, 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. 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 feed back loop that promotes the function of Dll1 MaSCs. Together, these findings reveal functionally important cross-talk between MaSCs and their macrophageal niche through Dll1/Notch-mediated signaling.

DOI10.1126/science.aan4153
Alternate JournalScience
PubMed ID29773667