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

doi:10.1126/science.aan4153

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

143 Citations (Scopus)

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 language	English
Journal	Science
Volume	360
Issue number	6396
DOIs	https://doi.org/10.1126/science.aan4153
Publication status	Published - 29 Jun 2018

Keywords

Animals
Cell Count
Female
Gene Knockout Techniques
Intercellular Signaling Peptides and Proteins/genetics
Ligands
Macrophages/cytology
Mammary Glands, Animal/cytology
Mice
Mice, Knockout
Morphogenesis
Receptors, Notch/metabolism
Signal Transduction
Stem Cell Niche/physiology
Stem Cells/cytology
Stromal Cells/cytology
Wnt Proteins/metabolism

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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). https://doi.org/10.1126/science.aan4153

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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.",

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author = "Rumela Chakrabarti and Toni Celi{\`a}-Terrassa and Sushil Kumar and Xiang Hang and Yong Wei and Abrar Choudhury and Julie Hwang and Jia Peng and Briana Nixon and Grady, {John J} and Christina DeCoste and Jie Gao and {van Es}, {Johan H} and Li, {Ming O} and Iannis Aifantis and Hans Clevers and Yibin Kang",

note = "Copyright {\textcopyright} 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2018",

month = jun,

day = "29",

doi = "10.1126/science.aan4153",

language = "English",

volume = "360",

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AU - Chakrabarti, Rumela

AU - Celià-Terrassa, Toni

AU - Kumar, Sushil

AU - Hang, Xiang

AU - Wei, Yong

AU - Choudhury, Abrar

AU - Hwang, Julie

AU - Peng, Jia

AU - Nixon, Briana

AU - Grady, John J

AU - DeCoste, Christina

AU - Gao, Jie

AU - van Es, Johan H

AU - Li, Ming O

AU - Aifantis, Iannis

AU - Clevers, Hans

AU - Kang, Yibin

PY - 2018/6/29

Y1 - 2018/6/29

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Count

KW - Female

KW - Gene Knockout Techniques

KW - Intercellular Signaling Peptides and Proteins/genetics

KW - Ligands

KW - Macrophages/cytology

KW - Mammary Glands, Animal/cytology

KW - Mice

KW - Mice, Knockout

KW - Morphogenesis

KW - Receptors, Notch/metabolism

KW - Signal Transduction

KW - Stem Cell Niche/physiology

KW - Stem Cells/cytology

KW - Stromal Cells/cytology

KW - Wnt Proteins/metabolism

U2 - 10.1126/science.aan4153

DO - 10.1126/science.aan4153

M3 - Article

C2 - 29773667

SN - 0036-8075

VL - 360

JO - Science

JF - Science

IS - 6396

ER -

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

Abstract

Keywords

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