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Science. 2018 Jun 29;360(6396). pii: eaan4153. doi: 10.1126/science.aan4153. Epub 2018 May 17.

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

Author information

1
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. ykang@princeton.edu rumela@vet.upenn.edu.
2
Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
4
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
5
Department of Pathology, NYU Langone Medical Center, New York City, NY 10016, USA.
6
Hubrecht Institute and University Medical Center Utrecht, Utrecht, Netherlands.
7
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.

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.

PMID:
29773667
DOI:
10.1126/science.aan4153
[Indexed for MEDLINE]

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