| Title | Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Chakrabarti, 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 |
| Journal | Science |
| Volume | 360 |
| Issue | 6396 |
| Date Published | 2018 06 29 |
| ISSN | 1095-9203 |
| Keywords | Animals, 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> |
| DOI | 10.1126/science.aan4153 |
| Alternate Journal | Science |
| PubMed ID | 29773667 |
| Grant List | R01 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 |
