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

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.

Authors:   Rumela Chakrabarti; Toni Celià-Terrassa; Sushil Kumar; Xiang Hang; Yong Wei; Abrar Choudhury; Julie Hwang; Jia Peng; Briana Nixon; John J. Grady; Christina DeCoste; Jie Gao; Johan H. van Es; Ming O. Li; Iannis Aifantis; Hans Clevers; Yibin Kang
Journal:   Science
Volume:   360
edition:   6396
Year:   2018
Pages:   eaan4153
DOI:   10.1126/science.aan4153
Publication date:   29-Jun-2018
Facts, background information, dossiers
  • ligands
  • interactions
  • homeostasis
  • Expression
  • environment
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