Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration
Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have n...
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Veröffentlicht in: | Cell 2011-06, Vol.145 (6), p.941-955 |
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description | Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations.
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► EpSCs express Wnts that activate Wnt signaling in McSCs and EpSCs at anagen onset ► Similar to EpSCs, Wnt activation in McSCs commits them to differentiation ► Forced Wnt activation in epithelial cells induces their endothelin upregulation ► Wnt activated EpSCs express endothelins that promote melanocyte proliferation |
doi_str_mv | 10.1016/j.cell.2011.05.004 |
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► EpSCs express Wnts that activate Wnt signaling in McSCs and EpSCs at anagen onset ► Similar to EpSCs, Wnt activation in McSCs commits them to differentiation ► Forced Wnt activation in epithelial cells induces their endothelin upregulation ► Wnt activated EpSCs express endothelins that promote melanocyte proliferation</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2011.05.004</identifier><identifier>PMID: 21663796</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>animal models ; Animals ; beta Catenin - metabolism ; Cell Differentiation ; Epithelial Cells - cytology ; Hair - cytology ; Hair - physiology ; Hair Diseases - metabolism ; Hair Diseases - pathology ; Hair Follicle - cytology ; hair follicles ; Humans ; melanocytes ; Melanocytes - cytology ; Mice ; Pigmentation ; population ; Regeneration ; Signal Transduction ; Skin - cytology ; Skin Physiological Phenomena ; stem cells ; Stem Cells - cytology ; Wnt Proteins - metabolism</subject><ispartof>Cell, 2011-06, Vol.145 (6), p.941-955</ispartof><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><rights>2011 Elsevier Inc. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c544t-f5ceb45fb42c65dcf6c565975a9ec8f6e9352617debeb9ad12b4442ea53125d23</citedby><cites>FETCH-LOGICAL-c544t-f5ceb45fb42c65dcf6c565975a9ec8f6e9352617debeb9ad12b4442ea53125d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cell.2011.05.004$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21663796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rabbani, Piul</creatorcontrib><creatorcontrib>Takeo, Makoto</creatorcontrib><creatorcontrib>Chou, WeiChin</creatorcontrib><creatorcontrib>Myung, Peggy</creatorcontrib><creatorcontrib>Bosenberg, Marcus</creatorcontrib><creatorcontrib>Chin, Lynda</creatorcontrib><creatorcontrib>Taketo, M. Mark</creatorcontrib><creatorcontrib>Ito, Mayumi</creatorcontrib><title>Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration</title><title>Cell</title><addtitle>Cell</addtitle><description>Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations.
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► EpSCs express Wnts that activate Wnt signaling in McSCs and EpSCs at anagen onset ► Similar to EpSCs, Wnt activation in McSCs commits them to differentiation ► Forced Wnt activation in epithelial cells induces their endothelin upregulation ► Wnt activated EpSCs express endothelins that promote melanocyte proliferation</description><subject>animal models</subject><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Cell Differentiation</subject><subject>Epithelial Cells - cytology</subject><subject>Hair - cytology</subject><subject>Hair - physiology</subject><subject>Hair Diseases - metabolism</subject><subject>Hair Diseases - pathology</subject><subject>Hair Follicle - cytology</subject><subject>hair follicles</subject><subject>Humans</subject><subject>melanocytes</subject><subject>Melanocytes - cytology</subject><subject>Mice</subject><subject>Pigmentation</subject><subject>population</subject><subject>Regeneration</subject><subject>Signal Transduction</subject><subject>Skin - cytology</subject><subject>Skin Physiological Phenomena</subject><subject>stem cells</subject><subject>Stem Cells - cytology</subject><subject>Wnt Proteins - metabolism</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFvFCEYhonR2G31D3hQbp5mBAaYncSYNJvWNqnR2DY9Ega-2bLOwArsJv33Mm5t9CIXDjzfw5vvRegNJTUlVH7Y1AbGsWaE0pqImhD-DC0o6dqK05Y9RwtCOlYtZcuP0HFKG0LIUgjxEh0xKmXTdnKBfqxCiNZ5ncHiU5PdXmcXPA4DvvMZO4_Pti7fw-j0iLW3-AuM2gfzkAFfZ5jwqkRI-NK77Ioj4W9uPYGfbRfaRfwd1uAh_pa-Qi8GPSZ4_XifoNvzs5vVRXX19fPl6vSqMoLzXA3CQM_F0HNmpLBmkEZI0bVCd2CWg4SuEUzS1kIPfactZT3nnIEWDWXCsuYEfTp4t7t-AmtKnKhHtY1u0vFBBe3Uvy_e3at12Kumk4yJtgjePwpi-LmDlNXk0rxr7SHsklq2TLBOclpIdiBNDClFGJ5-oUTNJamNmgfVXJIiQpWSytDbv_M9jfxppQDvDsCgg9Lr6JK6vS4GSeYjaVOIjwcCyh73DqJKxoE3YF0Ek5UN7n8JfgF2Ra7s</recordid><startdate>20110610</startdate><enddate>20110610</enddate><creator>Rabbani, Piul</creator><creator>Takeo, Makoto</creator><creator>Chou, WeiChin</creator><creator>Myung, Peggy</creator><creator>Bosenberg, Marcus</creator><creator>Chin, Lynda</creator><creator>Taketo, M. Mark</creator><creator>Ito, Mayumi</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110610</creationdate><title>Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration</title><author>Rabbani, Piul ; Takeo, Makoto ; Chou, WeiChin ; Myung, Peggy ; Bosenberg, Marcus ; Chin, Lynda ; Taketo, M. Mark ; Ito, Mayumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-f5ceb45fb42c65dcf6c565975a9ec8f6e9352617debeb9ad12b4442ea53125d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>animal models</topic><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>Cell Differentiation</topic><topic>Epithelial Cells - cytology</topic><topic>Hair - cytology</topic><topic>Hair - physiology</topic><topic>Hair Diseases - metabolism</topic><topic>Hair Diseases - pathology</topic><topic>Hair Follicle - cytology</topic><topic>hair follicles</topic><topic>Humans</topic><topic>melanocytes</topic><topic>Melanocytes - cytology</topic><topic>Mice</topic><topic>Pigmentation</topic><topic>population</topic><topic>Regeneration</topic><topic>Signal Transduction</topic><topic>Skin - cytology</topic><topic>Skin Physiological Phenomena</topic><topic>stem cells</topic><topic>Stem Cells - cytology</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rabbani, Piul</creatorcontrib><creatorcontrib>Takeo, Makoto</creatorcontrib><creatorcontrib>Chou, WeiChin</creatorcontrib><creatorcontrib>Myung, Peggy</creatorcontrib><creatorcontrib>Bosenberg, Marcus</creatorcontrib><creatorcontrib>Chin, Lynda</creatorcontrib><creatorcontrib>Taketo, M. Mark</creatorcontrib><creatorcontrib>Ito, Mayumi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rabbani, Piul</au><au>Takeo, Makoto</au><au>Chou, WeiChin</au><au>Myung, Peggy</au><au>Bosenberg, Marcus</au><au>Chin, Lynda</au><au>Taketo, M. Mark</au><au>Ito, Mayumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2011-06-10</date><risdate>2011</risdate><volume>145</volume><issue>6</issue><spage>941</spage><epage>955</epage><pages>941-955</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations.
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► EpSCs express Wnts that activate Wnt signaling in McSCs and EpSCs at anagen onset ► Similar to EpSCs, Wnt activation in McSCs commits them to differentiation ► Forced Wnt activation in epithelial cells induces their endothelin upregulation ► Wnt activated EpSCs express endothelins that promote melanocyte proliferation</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21663796</pmid><doi>10.1016/j.cell.2011.05.004</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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subjects | animal models Animals beta Catenin - metabolism Cell Differentiation Epithelial Cells - cytology Hair - cytology Hair - physiology Hair Diseases - metabolism Hair Diseases - pathology Hair Follicle - cytology hair follicles Humans melanocytes Melanocytes - cytology Mice Pigmentation population Regeneration Signal Transduction Skin - cytology Skin Physiological Phenomena stem cells Stem Cells - cytology Wnt Proteins - metabolism |
title | Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration |
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