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
Volume360
Issue6396
Date Published2018 06 29
ISSN1095-9203
KeywordsAnimals, Calcium-Binding Proteins, Cell Count, Female, Gene Knockout Techniques, Intercellular Signaling Peptides and Proteins, Ligands, Macrophages, Mammary Glands, Animal, Mice, Mice, Knockout, Morphogenesis, Receptors, Notch, Signal Transduction, Stem Cell Niche, Stem Cells, Stromal Cells, Wnt Proteins
Abstract

<p>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.</p>

DOI10.1126/science.aan4153
Alternate JournalScience
PubMed ID29773667
Grant ListR01 CA141062 / CA / NCI NIH HHS / United States
R01 CA198280 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
K22 CA193661 / CA / NCI NIH HHS / United States