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

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

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Article numbereaan4153
JournalScience
Volume360
Issue number6396
DOIs
StatePublished - Jun 29 2018

All Science Journal Classification (ASJC) codes

  • General

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    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. (2018). Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche. Science, 360(6396), [eaan4153]. https://doi.org/10.1126/science.aan4153