http://repository.iitr.ac.in/handle/123456789/20077| Title: | Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche |
| Authors: | Chakrabarti R. Celià-Terrassa T. Kumar, Sushil 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. |
| Published in: | Science |
| 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. |
| Citation: | Science, 360(6396) |
| URI: | https://doi.org/10.1126/science.aan4153 http://repository.iitr.ac.in/handle/123456789/20077 |
| Issue Date: | 2018 |
| Publisher: | American Association for the Advancement of Science |
| Keywords: | Notch ligand Dll1 Notch receptor Notch2 receptor Notch3 receptor unclassified drug Wnt protein Wnt10 protein Wnt16 protein Wnt3 protein Dlk1 protein, mouse ligand Notch receptor signal peptide Wnt protein cell gene expression genetic analysis ligand morphogenesis niche animal cell Article basal cell breast cell breast development breast epithelium cell cell count cell function cell lineage cell population cells by body anatomy coculture controlled study female lactation luminal cell lung alveolus macrophage molecular interaction morphogenesis mouse nonhuman Notch signaling pregnancy priority journal protein binding protein expression protein function regulatory mechanism stem cell Wnt signaling animal cytology gene knockout genetics growth, development and aging knockout mouse macrophage metabolism physiology signal transduction stem cell stem cell niche stroma cell udder Animals 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 |
| ISSN: | 368075 |
| Author Scopus IDs: | 16149432900 55207267200 57213855617 56577820400 47461837000 56577395200 55391053200 57220889759 55747199500 57202131172 17340437800 55702639800 7005206137 37069515500 6603005523 35594209900 7402784847 |
| Author Affiliations: | Chakrabarti, R., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States, Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA 19104, United States Celià-Terrassa, T., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States, Cancer Research Program, Hospital del Mar Research Institute (IMIM), Barcelona, Spain Kumar, S., Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA 19104, United States Hang, X., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States Wei, Y., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States Choudhury, A., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States Hwang, J., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States Peng, J., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States Nixon, B., Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States Grady, J.J., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States DeCoste, C., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States Gao, J., Department of Pathology, NYU Langone Medical Center, New York City, NY 10016, United States van Es, J.H., Hubrecht Institute, University Medical Center Utrecht, Utrecht, Netherlands Li, M.O., Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States Aifantis, I., Department of Pathology, NYU Langone Medical Center, New York City, NY 10016, United States Clevers, H., Department of Pathology, NYU Langone Medical Center, New York City, NY 10016, United States Kang, Y., Department of Molecular Biology, Princeton University, Princeton, NJ 08544, United States, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, United States |
| Funding Details: | National Cancer Institute, NCI: K22CA193661, P30CA008748, R01CA141062, R01CA198280 |
| Corresponding Author: | Chakrabarti, R.; Department of Molecular Biology, United States; email: rumela@vet.upenn.edu |
| Appears in Collections: | Journal Publications [BT] |
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