Authors: | Chakrabarti, R.; Celià-Terrassa, T.; Kumar, S.; Hang, X.; Wei, Y.; Choudhury, A.; Hwang, J.; Peng, J.; Nixon, B.; Grady, J. J.; DeCoste, C.; Gao, J.; van Es, J. H.; Li, M. O.; Aifantis, I.; Clevers, H.; Kang, Y. |
Article Title: | Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche |
Abstract: | 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. © 2017 The Authors. |
Keywords: | controlled study; protein expression; unclassified drug; nonhuman; genetic analysis; protein function; animal cell; mouse; cell function; gene expression; protein binding; notch receptor; morphogenesis; cell population; cell lineage; stem cell; basal cell; regulatory mechanism; ligand; pregnancy; cell count; molecular interaction; macrophage; wnt protein; breast cell; lactation; notch2 receptor; notch3 receptor; coculture; breast development; cell; wnt signaling; niche; wnt3 protein; notch signaling; lung alveolus; female; priority journal; article; breast epithelium cell; cells by body anatomy; wnt16 protein; notch ligand dll1; wnt10 protein; luminal cell |
Journal Title: | Science |
Volume: | 360 |
Issue: | 6396 |
ISSN: | 0036-8075 |
Publisher: | American Association for the Advancement of Science |
Date Published: | 2018-06-29 |
Start Page: | eaan4153 |
Language: | English |
DOI: | 10.1126/science.aan4153 |
PROVIDER: | scopus |
PUBMED: | 29773667 |
PMCID: | PMC7881440 |
DOI/URL: | |
Notes: | Article -- Export Date: 1 August 2018 -- Source: Scopus |