In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators
Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Here, we unfold genome-wide transcriptional and chromatin landscapes of β-catenin–TCF3/4–TLE circuitry, and genetically dissect their biological roles within the native HFSC niche. We show that during HFSC quiescence, TC...
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| Veröffentlicht in: | Nature cell biology 2014-02, Vol.16 (2), p.179-190 |
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| creator | Lien, Wen-Hui Polak, Lisa Lin, Mingyan Lay, Kenneth Zheng, Deyou Fuchs, Elaine |
| description | Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Here, we unfold genome-wide transcriptional and chromatin landscapes of β-catenin–TCF3/4–TLE circuitry, and genetically dissect their biological roles within the native HFSC niche. We show that during HFSC quiescence, TCF3, TCF4 and TLE (Groucho) bind coordinately and transcriptionally repress Wnt target genes. We also show that β-catenin is dispensable for HFSC viability, and if TCF3/4 levels are sufficiently reduced, it is dispensable for proliferation. However, β-catenin is essential to activate genes that launch hair follicle fate and suppress sebocyte fate determination. TCF3/4 deficiency mimics Wnt–β-catenin-dependent activation of these hair follicle fate targets; TCF3 overexpression parallels their TLE4-dependent suppression. Our studies unveil TCF3/4–TLE histone deacetylases as a repressive rheostat, whose action can be relieved by Wnt–β-catenin signalling. When TCF3/4 and TLE levels are high, HFSCs can maintain stemness, but remain quiescent. When these levels drop or when Wnt–β-catenin levels rise, this balance is shifted and hair regeneration initiates.
Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Fuchs and colleagues use a genome-wide survey to discover that Wnt effectors TCF3, TCF4 and Groucho (TLE) coordinately repress Wnt target genes. They find that although β-catenin is dispensable for HSFC viability and proliferation, it is essential to relieve this repression to initiate hair follicle fate during the hair regeneration cycle. |
| doi_str_mv | 10.1038/ncb2903 |
| format | Article |
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Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Fuchs and colleagues use a genome-wide survey to discover that Wnt effectors TCF3, TCF4 and Groucho (TLE) coordinately repress Wnt target genes. They find that although β-catenin is dispensable for HSFC viability and proliferation, it is essential to relieve this repression to initiate hair follicle fate during the hair regeneration cycle.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb2903</identifier><identifier>PMID: 24463605</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136/334/1874/345 ; 631/136/532/1360 ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; beta Catenin - physiology ; Cancer Research ; Cell Biology ; Cell Differentiation ; Cellular signal transduction ; Developmental Biology ; Genetic aspects ; Hair ; Hair Follicle - cytology ; Hair Follicle - metabolism ; Hair follicles ; Life Sciences ; Mice ; Mice, Knockout ; Physiological aspects ; Regeneration ; Signal Transduction ; Stem Cells ; Transcription Factor 4 ; Transcription, Genetic ; Wnt Proteins - metabolism</subject><ispartof>Nature cell biology, 2014-02, Vol.16 (2), p.179-190</ispartof><rights>Springer Nature Limited 2014</rights><rights>COPYRIGHT 2014 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2014</rights><rights>2014 Macmillan Publishers Limited. All rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c630t-72a75de201598433d0e7085cbe9725557102efea2d253e90afd81d54e718b6fd3</citedby><cites>FETCH-LOGICAL-c630t-72a75de201598433d0e7085cbe9725557102efea2d253e90afd81d54e718b6fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncb2903$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ncb2903$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24463605$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lien, Wen-Hui</creatorcontrib><creatorcontrib>Polak, Lisa</creatorcontrib><creatorcontrib>Lin, Mingyan</creatorcontrib><creatorcontrib>Lay, Kenneth</creatorcontrib><creatorcontrib>Zheng, Deyou</creatorcontrib><creatorcontrib>Fuchs, Elaine</creatorcontrib><title>In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Here, we unfold genome-wide transcriptional and chromatin landscapes of β-catenin–TCF3/4–TLE circuitry, and genetically dissect their biological roles within the native HFSC niche. We show that during HFSC quiescence, TCF3, TCF4 and TLE (Groucho) bind coordinately and transcriptionally repress Wnt target genes. We also show that β-catenin is dispensable for HFSC viability, and if TCF3/4 levels are sufficiently reduced, it is dispensable for proliferation. However, β-catenin is essential to activate genes that launch hair follicle fate and suppress sebocyte fate determination. TCF3/4 deficiency mimics Wnt–β-catenin-dependent activation of these hair follicle fate targets; TCF3 overexpression parallels their TLE4-dependent suppression. Our studies unveil TCF3/4–TLE histone deacetylases as a repressive rheostat, whose action can be relieved by Wnt–β-catenin signalling. When TCF3/4 and TLE levels are high, HFSCs can maintain stemness, but remain quiescent. When these levels drop or when Wnt–β-catenin levels rise, this balance is shifted and hair regeneration initiates.
Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Fuchs and colleagues use a genome-wide survey to discover that Wnt effectors TCF3, TCF4 and Groucho (TLE) coordinately repress Wnt target genes. They find that although β-catenin is dispensable for HSFC viability and proliferation, it is essential to relieve this repression to initiate hair follicle fate during the hair regeneration cycle.</description><subject>631/136/334/1874/345</subject><subject>631/136/532/1360</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>beta Catenin - physiology</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Differentiation</subject><subject>Cellular signal transduction</subject><subject>Developmental Biology</subject><subject>Genetic aspects</subject><subject>Hair</subject><subject>Hair Follicle - cytology</subject><subject>Hair Follicle - metabolism</subject><subject>Hair follicles</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Physiological aspects</subject><subject>Regeneration</subject><subject>Signal Transduction</subject><subject>Stem Cells</subject><subject>Transcription Factor 4</subject><subject>Transcription, Genetic</subject><subject>Wnt Proteins - 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Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lien, Wen-Hui</au><au>Polak, Lisa</au><au>Lin, Mingyan</au><au>Lay, Kenneth</au><au>Zheng, Deyou</au><au>Fuchs, Elaine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>16</volume><issue>2</issue><spage>179</spage><epage>190</epage><pages>179-190</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Here, we unfold genome-wide transcriptional and chromatin landscapes of β-catenin–TCF3/4–TLE circuitry, and genetically dissect their biological roles within the native HFSC niche. We show that during HFSC quiescence, TCF3, TCF4 and TLE (Groucho) bind coordinately and transcriptionally repress Wnt target genes. We also show that β-catenin is dispensable for HFSC viability, and if TCF3/4 levels are sufficiently reduced, it is dispensable for proliferation. However, β-catenin is essential to activate genes that launch hair follicle fate and suppress sebocyte fate determination. TCF3/4 deficiency mimics Wnt–β-catenin-dependent activation of these hair follicle fate targets; TCF3 overexpression parallels their TLE4-dependent suppression. Our studies unveil TCF3/4–TLE histone deacetylases as a repressive rheostat, whose action can be relieved by Wnt–β-catenin signalling. When TCF3/4 and TLE levels are high, HFSCs can maintain stemness, but remain quiescent. When these levels drop or when Wnt–β-catenin levels rise, this balance is shifted and hair regeneration initiates.
Hair follicle stem cells (HFSCs) regenerate hair in response to Wnt signalling. Fuchs and colleagues use a genome-wide survey to discover that Wnt effectors TCF3, TCF4 and Groucho (TLE) coordinately repress Wnt target genes. They find that although β-catenin is dispensable for HSFC viability and proliferation, it is essential to relieve this repression to initiate hair follicle fate during the hair regeneration cycle.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24463605</pmid><doi>10.1038/ncb2903</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Nature cell biology, 2014-02, Vol.16 (2), p.179-190 |
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| subjects | 631/136/334/1874/345 631/136/532/1360 Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism Basic Helix-Loop-Helix Transcription Factors - metabolism beta Catenin - physiology Cancer Research Cell Biology Cell Differentiation Cellular signal transduction Developmental Biology Genetic aspects Hair Hair Follicle - cytology Hair Follicle - metabolism Hair follicles Life Sciences Mice Mice, Knockout Physiological aspects Regeneration Signal Transduction Stem Cells Transcription Factor 4 Transcription, Genetic Wnt Proteins - metabolism |
| title | In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators |
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