Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration
Urothelium is the protective lining of the urinary tract. The mechanisms underlying urothelial formation and maintenance are largely unknown. Here, we report the stage-specific roles of PRC2 epigenetic regulators in embryonic and adult urothelial progenitors. Without Eed, the obligatory subunit of P...
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| Veröffentlicht in: | Development (Cambridge) 2017-02, Vol.144 (3), p.400-408 |
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| description | Urothelium is the protective lining of the urinary tract. The mechanisms underlying urothelial formation and maintenance are largely unknown. Here, we report the stage-specific roles of PRC2 epigenetic regulators in embryonic and adult urothelial progenitors. Without Eed, the obligatory subunit of PRC2, embryonic urothelial progenitors demonstrate reduced proliferation with concomitant dysregulation of genes including Cdkn2a (p16), Cdkn2b (p15) and Shh. These mutants display premature differentiation of keratin 5-positive (Krt5
) basal cells and ectopic expression of squamous-like differentiation markers. Deletion of Ezh2, the major enzymatic component of PRC2, causes upregulation of Upk3a
superficial cells. Unexpectedly, Eed and Eed/Ezh2 double mutants exhibit delayed superficial cell differentiation. Furthermore, Eed regulates the proliferative and regenerative capacity of adult urothelial progenitors and prevents precocious differentiation. Collectively, these findings uncover the epigenetic mechanism by which PRC2 controls urothelial progenitor cell fate and the timing of differentiation, and further suggest an epigenetic basis of urothelial maintenance and regeneration. |
| doi_str_mv | 10.1242/dev.143958 |
| format | Article |
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) basal cells and ectopic expression of squamous-like differentiation markers. Deletion of Ezh2, the major enzymatic component of PRC2, causes upregulation of Upk3a
superficial cells. Unexpectedly, Eed and Eed/Ezh2 double mutants exhibit delayed superficial cell differentiation. Furthermore, Eed regulates the proliferative and regenerative capacity of adult urothelial progenitors and prevents precocious differentiation. Collectively, these findings uncover the epigenetic mechanism by which PRC2 controls urothelial progenitor cell fate and the timing of differentiation, and further suggest an epigenetic basis of urothelial maintenance and regeneration.</description><identifier>ISSN: 0950-1991</identifier><identifier>EISSN: 1477-9129</identifier><identifier>DOI: 10.1242/dev.143958</identifier><identifier>PMID: 28049658</identifier><language>eng</language><publisher>England: The Company of Biologists Ltd</publisher><subject>Adult Stem Cells - cytology ; Adult Stem Cells - physiology ; Animals ; Basal cells ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Cell fate ; Cell proliferation ; Clonal deletion ; Ectopic expression ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - physiology ; Embryos ; Epigenesis, Genetic ; Epigenetics ; Female ; Gene Expression Regulation, Developmental ; Hedgehog Proteins - genetics ; Hedgehog Proteins - physiology ; Keratin ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Mutation ; Polycomb group proteins ; Polycomb Repressive Complex 2 - chemistry ; Polycomb Repressive Complex 2 - deficiency ; Polycomb Repressive Complex 2 - genetics ; Polycomb Repressive Complex 2 - physiology ; Progenitor cells ; Protein Subunits ; Regeneration - genetics ; Regeneration - physiology ; Stem Cells and Regeneration ; Urinary bladder ; Urinary Bladder - embryology ; Urinary Bladder - growth & development ; Urinary Bladder - physiology ; Urinary tract ; Urothelium ; Urothelium - embryology ; Urothelium - growth & development ; Urothelium - physiology</subject><ispartof>Development (Cambridge), 2017-02, Vol.144 (3), p.400-408</ispartof><rights>2017. Published by The Company of Biologists Ltd.</rights><rights>Copyright The Company of Biologists Ltd Feb 1, 2017</rights><rights>2017. Published by The Company of Biologists Ltd 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-6dfaf9f295a132361f665412b90ed4c4e35a37f1b8e9472f9c9288c469b58a493</citedby><cites>FETCH-LOGICAL-c439t-6dfaf9f295a132361f665412b90ed4c4e35a37f1b8e9472f9c9288c469b58a493</cites><orcidid>0000-0002-3072-0573 ; 0000-0002-2772-7264</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3678,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28049658$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Chunming</creatorcontrib><creatorcontrib>Balsara, Zarine R</creatorcontrib><creatorcontrib>Hill, Warren G</creatorcontrib><creatorcontrib>Li, Xue</creatorcontrib><title>Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration</title><title>Development (Cambridge)</title><addtitle>Development</addtitle><description>Urothelium is the protective lining of the urinary tract. The mechanisms underlying urothelial formation and maintenance are largely unknown. Here, we report the stage-specific roles of PRC2 epigenetic regulators in embryonic and adult urothelial progenitors. Without Eed, the obligatory subunit of PRC2, embryonic urothelial progenitors demonstrate reduced proliferation with concomitant dysregulation of genes including Cdkn2a (p16), Cdkn2b (p15) and Shh. These mutants display premature differentiation of keratin 5-positive (Krt5
) basal cells and ectopic expression of squamous-like differentiation markers. Deletion of Ezh2, the major enzymatic component of PRC2, causes upregulation of Upk3a
superficial cells. Unexpectedly, Eed and Eed/Ezh2 double mutants exhibit delayed superficial cell differentiation. Furthermore, Eed regulates the proliferative and regenerative capacity of adult urothelial progenitors and prevents precocious differentiation. Collectively, these findings uncover the epigenetic mechanism by which PRC2 controls urothelial progenitor cell fate and the timing of differentiation, and further suggest an epigenetic basis of urothelial maintenance and regeneration.</description><subject>Adult Stem Cells - cytology</subject><subject>Adult Stem Cells - physiology</subject><subject>Animals</subject><subject>Basal cells</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Cell fate</subject><subject>Cell proliferation</subject><subject>Clonal deletion</subject><subject>Ectopic expression</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - physiology</subject><subject>Embryos</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Hedgehog Proteins - genetics</subject><subject>Hedgehog Proteins - physiology</subject><subject>Keratin</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Mutation</subject><subject>Polycomb group proteins</subject><subject>Polycomb Repressive Complex 2 - chemistry</subject><subject>Polycomb Repressive Complex 2 - deficiency</subject><subject>Polycomb Repressive Complex 2 - genetics</subject><subject>Polycomb Repressive Complex 2 - physiology</subject><subject>Progenitor cells</subject><subject>Protein Subunits</subject><subject>Regeneration - genetics</subject><subject>Regeneration - physiology</subject><subject>Stem Cells and Regeneration</subject><subject>Urinary bladder</subject><subject>Urinary Bladder - embryology</subject><subject>Urinary Bladder - growth & development</subject><subject>Urinary Bladder - physiology</subject><subject>Urinary tract</subject><subject>Urothelium</subject><subject>Urothelium - embryology</subject><subject>Urothelium - growth & development</subject><subject>Urothelium - physiology</subject><issn>0950-1991</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1rFTEUhoNY7LW68QdIwE0RpuZ7ko1QSv2AQhfqOmQyJ7cpM8mYzFztv3duby3qylVIzsOTc86L0CtKzigT7F0PuzMquJH6CdpQ0baNocw8RRtiJGmoMfQYPa_1lhDCVds-Q8dME2GU1Bv048vsttBgl3pcl25JcW7qBD6G6HFYkp9jThXngKc83Pk8drjAVKDWuAO83qcBfmKGY8Ld4PoeCl5Knm9giG7AIZfR7Q33_gJbSFDuH16go-CGCi8fzhP07cPl14tPzdX1x88X51eNXweaG9UHF0xgRjrKGVc0KCUFZZ0h0AsvgEvH20A7DUa0LBhvmNZeKNNJ7YThJ-j9wTst3Qi9hzQXN9ipxNGVO5tdtH9XUryx27yzkguqCV0Fpw-Ckr8vUGc7xuphGFyCvFRLtdKcta3g_4FKybkg7b6tN_-gt3kpad2EpUavXyvD9tTbA-VLrrVAeOybEruP3q7R20P0K_z6z0kf0d9Z818b1auP</recordid><startdate>20170201</startdate><enddate>20170201</enddate><creator>Guo, Chunming</creator><creator>Balsara, Zarine R</creator><creator>Hill, Warren G</creator><creator>Li, Xue</creator><general>The Company of Biologists Ltd</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>7QP</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3072-0573</orcidid><orcidid>https://orcid.org/0000-0002-2772-7264</orcidid></search><sort><creationdate>20170201</creationdate><title>Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration</title><author>Guo, Chunming ; Balsara, Zarine R ; Hill, Warren G ; Li, Xue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-6dfaf9f295a132361f665412b90ed4c4e35a37f1b8e9472f9c9288c469b58a493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult Stem Cells - cytology</topic><topic>Adult Stem Cells - physiology</topic><topic>Animals</topic><topic>Basal cells</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - physiology</topic><topic>Cell fate</topic><topic>Cell proliferation</topic><topic>Clonal deletion</topic><topic>Ectopic expression</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - physiology</topic><topic>Embryos</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Hedgehog Proteins - genetics</topic><topic>Hedgehog Proteins - physiology</topic><topic>Keratin</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Mutation</topic><topic>Polycomb group proteins</topic><topic>Polycomb Repressive Complex 2 - chemistry</topic><topic>Polycomb Repressive Complex 2 - deficiency</topic><topic>Polycomb Repressive Complex 2 - genetics</topic><topic>Polycomb Repressive Complex 2 - physiology</topic><topic>Progenitor cells</topic><topic>Protein Subunits</topic><topic>Regeneration - genetics</topic><topic>Regeneration - physiology</topic><topic>Stem Cells and Regeneration</topic><topic>Urinary bladder</topic><topic>Urinary Bladder - embryology</topic><topic>Urinary Bladder - growth & development</topic><topic>Urinary Bladder - physiology</topic><topic>Urinary tract</topic><topic>Urothelium</topic><topic>Urothelium - embryology</topic><topic>Urothelium - growth & development</topic><topic>Urothelium - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Chunming</creatorcontrib><creatorcontrib>Balsara, Zarine R</creatorcontrib><creatorcontrib>Hill, Warren G</creatorcontrib><creatorcontrib>Li, Xue</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Chunming</au><au>Balsara, Zarine R</au><au>Hill, Warren G</au><au>Li, Xue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2017-02-01</date><risdate>2017</risdate><volume>144</volume><issue>3</issue><spage>400</spage><epage>408</epage><pages>400-408</pages><issn>0950-1991</issn><eissn>1477-9129</eissn><abstract>Urothelium is the protective lining of the urinary tract. The mechanisms underlying urothelial formation and maintenance are largely unknown. Here, we report the stage-specific roles of PRC2 epigenetic regulators in embryonic and adult urothelial progenitors. Without Eed, the obligatory subunit of PRC2, embryonic urothelial progenitors demonstrate reduced proliferation with concomitant dysregulation of genes including Cdkn2a (p16), Cdkn2b (p15) and Shh. These mutants display premature differentiation of keratin 5-positive (Krt5
) basal cells and ectopic expression of squamous-like differentiation markers. Deletion of Ezh2, the major enzymatic component of PRC2, causes upregulation of Upk3a
superficial cells. Unexpectedly, Eed and Eed/Ezh2 double mutants exhibit delayed superficial cell differentiation. Furthermore, Eed regulates the proliferative and regenerative capacity of adult urothelial progenitors and prevents precocious differentiation. Collectively, these findings uncover the epigenetic mechanism by which PRC2 controls urothelial progenitor cell fate and the timing of differentiation, and further suggest an epigenetic basis of urothelial maintenance and regeneration.</abstract><cop>England</cop><pub>The Company of Biologists Ltd</pub><pmid>28049658</pmid><doi>10.1242/dev.143958</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3072-0573</orcidid><orcidid>https://orcid.org/0000-0002-2772-7264</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0950-1991 |
| ispartof | Development (Cambridge), 2017-02, Vol.144 (3), p.400-408 |
| issn | 0950-1991 1477-9129 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5341801 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Adult Stem Cells - cytology Adult Stem Cells - physiology Animals Basal cells Cell Differentiation - genetics Cell Differentiation - physiology Cell fate Cell proliferation Clonal deletion Ectopic expression Embryonic Stem Cells - cytology Embryonic Stem Cells - physiology Embryos Epigenesis, Genetic Epigenetics Female Gene Expression Regulation, Developmental Hedgehog Proteins - genetics Hedgehog Proteins - physiology Keratin Male Mice Mice, Knockout Mice, Transgenic Mutation Polycomb group proteins Polycomb Repressive Complex 2 - chemistry Polycomb Repressive Complex 2 - deficiency Polycomb Repressive Complex 2 - genetics Polycomb Repressive Complex 2 - physiology Progenitor cells Protein Subunits Regeneration - genetics Regeneration - physiology Stem Cells and Regeneration Urinary bladder Urinary Bladder - embryology Urinary Bladder - growth & development Urinary Bladder - physiology Urinary tract Urothelium Urothelium - embryology Urothelium - growth & development Urothelium - physiology |
| title | Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration |
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