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 mou...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2018-06, Vol.360 (6396) |
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| creator | Chakrabarti, Rumela Celià-Terrassa, Toni Kumar, Sushil Hang, Xiang Wei, Yong Choudhury, Abrar Hwang, Julie Peng, Jia Nixon, Briana Grady, John J DeCoste, Christina Gao, Jie van Es, Johan H Li, Ming O Aifantis, Iannis Clevers, Hans Kang, Yibin |
| description | 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. |
| doi_str_mv | 10.1126/science.aan4153 |
| format | Article |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.aan4153</identifier><identifier>PMID: 29773667</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Alveoli ; Animal models ; Animals ; Breast cancer ; Calcium-Binding Proteins ; Cancer ; Cell Count ; Cell fate ; Cell self-renewal ; Clonal deletion ; Coupling (molecular) ; Crosstalk ; Enrichment ; Epithelial cells ; Feedback (Response) ; Feedback loops ; Female ; Fibroblasts ; Gene Knockout Techniques ; Homeostasis ; Immune system ; Individualized Instruction ; Intercellular Signaling Peptides and Proteins - genetics ; Intercellular Signaling Peptides and Proteins - metabolism ; Lactation ; Ligands ; Macrophages ; Macrophages - cytology ; Macrophages - physiology ; Mammary gland ; Mammary Glands, Animal - cytology ; Mammary Glands, Animal - growth & development ; Mammary Glands, Animal - metabolism ; Mice ; Mice, Knockout ; Molecular chains ; Morphogenesis ; Notch protein ; Notch2 protein ; Notch3 protein ; Organs ; Pharmacology ; Populations ; Pregnancy ; Receptors ; Receptors, Notch - metabolism ; Regeneration ; Signal Transduction ; Signaling ; Stem Cell Niche - physiology ; Stem cell transplantation ; Stem cells ; Stem Cells - cytology ; Stem Cells - physiology ; Stromal Cells - cytology ; Stromal Cells - physiology ; Survival ; Tissue engineering ; Wnt protein ; Wnt Proteins - metabolism</subject><ispartof>Science (American Association for the Advancement of Science), 2018-06, Vol.360 (6396)</ispartof><rights>Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.</rights><rights>Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-f627f9a17d2ca1fd0beca2147aeb638fd98730fd61d85b827625d04caae138fb3</citedby><cites>FETCH-LOGICAL-c432t-f627f9a17d2ca1fd0beca2147aeb638fd98730fd61d85b827625d04caae138fb3</cites><orcidid>0000-0001-6684-7958 ; 0000-0003-4002-0244 ; 0000-0002-1626-6730 ; 0000-0002-0955-4435 ; 0000-0002-1034-649X ; 0000-0003-3779-5129 ; 0000-0003-2124-8737 ; 0000-0002-0615-8744 ; 0000-0002-3077-5582 ; 0000-0002-1383-0535 ; 0000-0001-6857-1035</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,2871,2872,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29773667$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chakrabarti, Rumela</creatorcontrib><creatorcontrib>Celià-Terrassa, Toni</creatorcontrib><creatorcontrib>Kumar, Sushil</creatorcontrib><creatorcontrib>Hang, Xiang</creatorcontrib><creatorcontrib>Wei, Yong</creatorcontrib><creatorcontrib>Choudhury, Abrar</creatorcontrib><creatorcontrib>Hwang, Julie</creatorcontrib><creatorcontrib>Peng, Jia</creatorcontrib><creatorcontrib>Nixon, Briana</creatorcontrib><creatorcontrib>Grady, John J</creatorcontrib><creatorcontrib>DeCoste, Christina</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>van Es, Johan H</creatorcontrib><creatorcontrib>Li, Ming O</creatorcontrib><creatorcontrib>Aifantis, Iannis</creatorcontrib><creatorcontrib>Clevers, Hans</creatorcontrib><creatorcontrib>Kang, Yibin</creatorcontrib><title>Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Alveoli</subject><subject>Animal models</subject><subject>Animals</subject><subject>Breast cancer</subject><subject>Calcium-Binding Proteins</subject><subject>Cancer</subject><subject>Cell Count</subject><subject>Cell fate</subject><subject>Cell self-renewal</subject><subject>Clonal deletion</subject><subject>Coupling (molecular)</subject><subject>Crosstalk</subject><subject>Enrichment</subject><subject>Epithelial cells</subject><subject>Feedback (Response)</subject><subject>Feedback loops</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gene Knockout Techniques</subject><subject>Homeostasis</subject><subject>Immune system</subject><subject>Individualized Instruction</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Lactation</subject><subject>Ligands</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - physiology</subject><subject>Mammary gland</subject><subject>Mammary Glands, Animal - cytology</subject><subject>Mammary Glands, Animal - growth & development</subject><subject>Mammary Glands, Animal - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular chains</subject><subject>Morphogenesis</subject><subject>Notch protein</subject><subject>Notch2 protein</subject><subject>Notch3 protein</subject><subject>Organs</subject><subject>Pharmacology</subject><subject>Populations</subject><subject>Pregnancy</subject><subject>Receptors</subject><subject>Receptors, Notch - metabolism</subject><subject>Regeneration</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Stem Cell Niche - physiology</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - physiology</subject><subject>Stromal Cells - cytology</subject><subject>Stromal Cells - physiology</subject><subject>Survival</subject><subject>Tissue engineering</subject><subject>Wnt protein</subject><subject>Wnt Proteins - metabolism</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkD1PwzAQhi0EoqUwsyFLLCxp_ZHY8YjKp1TBAhNDdHEuTUo-SpwI8e9xaGFguuF93tPdQ8g5Z3POhVo4W2JjcQ7QhDySB2TKmYkCI5g8JFPGpApipqMJOXFuw5jPjDwmE2G0lkrpKXl7antb0KpcQ5PRm6ritMashB4dtV3rXNBD9U5T7D8RG1pDXUP3RV2PNbVYVY6Ovb5AH3l-W8AaoaJNaQs8JUc5VA7P9nNGXu9uX5YPwer5_nF5vQpsKEUf5Ero3ADXmbDA84ylaEHwUAOmSsZ5ZmItWZ4pnsVRGgutRJSx0AIg93EqZ-Rqt3fbtR8Duj6pSzceBw22g0sEC7mSggnh0ct_6KYdusZf5ynFQ8O4MZ5a7KgfAx3mybYrx78TzpLRe7L3nuy9-8bFfu-Qen9__K9o-Q2I14C9</recordid><startdate>20180629</startdate><enddate>20180629</enddate><creator>Chakrabarti, Rumela</creator><creator>Celià-Terrassa, Toni</creator><creator>Kumar, Sushil</creator><creator>Hang, Xiang</creator><creator>Wei, Yong</creator><creator>Choudhury, Abrar</creator><creator>Hwang, Julie</creator><creator>Peng, Jia</creator><creator>Nixon, Briana</creator><creator>Grady, John J</creator><creator>DeCoste, Christina</creator><creator>Gao, Jie</creator><creator>van Es, Johan H</creator><creator>Li, Ming O</creator><creator>Aifantis, Iannis</creator><creator>Clevers, Hans</creator><creator>Kang, Yibin</creator><general>The American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6684-7958</orcidid><orcidid>https://orcid.org/0000-0003-4002-0244</orcidid><orcidid>https://orcid.org/0000-0002-1626-6730</orcidid><orcidid>https://orcid.org/0000-0002-0955-4435</orcidid><orcidid>https://orcid.org/0000-0002-1034-649X</orcidid><orcidid>https://orcid.org/0000-0003-3779-5129</orcidid><orcidid>https://orcid.org/0000-0003-2124-8737</orcidid><orcidid>https://orcid.org/0000-0002-0615-8744</orcidid><orcidid>https://orcid.org/0000-0002-3077-5582</orcidid><orcidid>https://orcid.org/0000-0002-1383-0535</orcidid><orcidid>https://orcid.org/0000-0001-6857-1035</orcidid></search><sort><creationdate>20180629</creationdate><title>Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche</title><author>Chakrabarti, Rumela ; Celià-Terrassa, Toni ; Kumar, Sushil ; Hang, Xiang ; Wei, Yong ; Choudhury, Abrar ; Hwang, Julie ; Peng, Jia ; Nixon, Briana ; Grady, John J ; DeCoste, Christina ; Gao, Jie ; van Es, Johan H ; Li, Ming O ; Aifantis, Iannis ; Clevers, Hans ; Kang, Yibin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-f627f9a17d2ca1fd0beca2147aeb638fd98730fd61d85b827625d04caae138fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Alveoli</topic><topic>Animal models</topic><topic>Animals</topic><topic>Breast cancer</topic><topic>Calcium-Binding Proteins</topic><topic>Cancer</topic><topic>Cell Count</topic><topic>Cell fate</topic><topic>Cell self-renewal</topic><topic>Clonal deletion</topic><topic>Coupling (molecular)</topic><topic>Crosstalk</topic><topic>Enrichment</topic><topic>Epithelial cells</topic><topic>Feedback (Response)</topic><topic>Feedback loops</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Gene Knockout Techniques</topic><topic>Homeostasis</topic><topic>Immune system</topic><topic>Individualized Instruction</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Lactation</topic><topic>Ligands</topic><topic>Macrophages</topic><topic>Macrophages - cytology</topic><topic>Macrophages - physiology</topic><topic>Mammary gland</topic><topic>Mammary Glands, Animal - cytology</topic><topic>Mammary Glands, Animal - growth & development</topic><topic>Mammary Glands, Animal - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular chains</topic><topic>Morphogenesis</topic><topic>Notch protein</topic><topic>Notch2 protein</topic><topic>Notch3 protein</topic><topic>Organs</topic><topic>Pharmacology</topic><topic>Populations</topic><topic>Pregnancy</topic><topic>Receptors</topic><topic>Receptors, Notch - metabolism</topic><topic>Regeneration</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Stem Cell Niche - physiology</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - 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| ispartof | Science (American Association for the Advancement of Science), 2018-06, Vol.360 (6396) |
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| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Alveoli Animal models Animals Breast cancer Calcium-Binding Proteins Cancer Cell Count Cell fate Cell self-renewal Clonal deletion Coupling (molecular) Crosstalk Enrichment Epithelial cells Feedback (Response) Feedback loops Female Fibroblasts Gene Knockout Techniques Homeostasis Immune system Individualized Instruction Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Lactation Ligands Macrophages Macrophages - cytology Macrophages - physiology Mammary gland Mammary Glands, Animal - cytology Mammary Glands, Animal - growth & development Mammary Glands, Animal - metabolism Mice Mice, Knockout Molecular chains Morphogenesis Notch protein Notch2 protein Notch3 protein Organs Pharmacology Populations Pregnancy Receptors Receptors, Notch - metabolism Regeneration Signal Transduction Signaling Stem Cell Niche - physiology Stem cell transplantation Stem cells Stem Cells - cytology Stem Cells - physiology Stromal Cells - cytology Stromal Cells - physiology Survival Tissue engineering Wnt protein Wnt Proteins - metabolism |
| title | Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche |
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