Fibroblast heterogeneity: implications for human disease
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial locat...
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Veröffentlicht in: | The Journal of clinical investigation 2018-01, Vol.128 (1), p.26-35 |
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description | Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications. |
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Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI93555</identifier><identifier>PMID: 29293096</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Aging ; Animals ; Arthritis ; Biomedical research ; Cancer ; Collagen ; Connective tissue ; Dermis ; Dermis - metabolism ; Dermis - pathology ; Disease ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Extracellular matrix ; Fibroblasts ; Fibroblasts - classification ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Gene expression ; Gene Expression Regulation, Neoplastic ; Humans ; Review Series ; Rodents ; Skin ; Skin Neoplasms - classification ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Specialization ; Therapeutic applications ; Transcription ; Transcription, Genetic ; Wound healing</subject><ispartof>The Journal of clinical investigation, 2018-01, Vol.128 (1), p.26-35</ispartof><rights>COPYRIGHT 2018 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Jan 2018</rights><rights>Copyright © 2018, American Society for Clinical Investigation 2018 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-766796a487827f354025970b78f898989414a7a04afc5ff4e14d21dba87b93523</citedby><cites>FETCH-LOGICAL-c470t-766796a487827f354025970b78f898989414a7a04afc5ff4e14d21dba87b93523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749540/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749540/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29293096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lynch, Magnus D</creatorcontrib><creatorcontrib>Watt, Fiona M</creatorcontrib><title>Fibroblast heterogeneity: implications for human disease</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.</description><subject>Aging</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Biomedical research</subject><subject>Cancer</subject><subject>Collagen</subject><subject>Connective tissue</subject><subject>Dermis</subject><subject>Dermis - metabolism</subject><subject>Dermis - pathology</subject><subject>Disease</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Fibroblasts - classification</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - pathology</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Review Series</subject><subject>Rodents</subject><subject>Skin</subject><subject>Skin Neoplasms - classification</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Specialization</subject><subject>Therapeutic applications</subject><subject>Transcription</subject><subject>Transcription, Genetic</subject><subject>Wound healing</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkVtLxDAQhYMoul7AXyAFQXyp5tokPgiyeGXBF30OaTfdRtJmTVJh_71d3V0vzMM8zMeZOXMAOEbwAiGOL5_Gj5IwxrbACDEmcoGJ2AYjCDHKJSdiD-zH-AYhopTRXbCHJZYEymIExJ0tgy-djilrTDLBz0xnbFpcZbadO1vpZH0Xs9qHrOlb3WVTG42O5hDs1NpFc7TqB-D17vZl_JBPnu8fxzeTvKIcppwXBZeFpoILzGvCKMRMclhyUQu5LIqo5hpSXVesrqlBdIrRtNSCl4MlTA7A9bfuvC9bM61Ml4J2ah5sq8NCeW3V30lnGzXzH4pxKod1g8D5SiD4997EpFobK-Oc7ozvo0JSEEEFRmhAT_-hb74P3WBvSRVQYEqW1Nk3NdPOqMZol5roXf_1KHUz3AwLAiH92VwFH2Mw9eZqBNUyN7XObUBPfrvcgOugyCeI5ZBx</recordid><startdate>20180102</startdate><enddate>20180102</enddate><creator>Lynch, Magnus D</creator><creator>Watt, Fiona M</creator><general>American Society for Clinical Investigation</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180102</creationdate><title>Fibroblast heterogeneity: implications for human disease</title><author>Lynch, Magnus D ; Watt, Fiona M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-766796a487827f354025970b78f898989414a7a04afc5ff4e14d21dba87b93523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Arthritis</topic><topic>Biomedical research</topic><topic>Cancer</topic><topic>Collagen</topic><topic>Connective tissue</topic><topic>Dermis</topic><topic>Dermis - metabolism</topic><topic>Dermis - pathology</topic><topic>Disease</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Extracellular matrix</topic><topic>Fibroblasts</topic><topic>Fibroblasts - classification</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - pathology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Review Series</topic><topic>Rodents</topic><topic>Skin</topic><topic>Skin Neoplasms - classification</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Specialization</topic><topic>Therapeutic applications</topic><topic>Transcription</topic><topic>Transcription, Genetic</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lynch, Magnus D</creatorcontrib><creatorcontrib>Watt, Fiona M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lynch, Magnus D</au><au>Watt, Fiona M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fibroblast heterogeneity: implications for human disease</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2018-01-02</date><risdate>2018</risdate><volume>128</volume><issue>1</issue><spage>26</spage><epage>35</epage><pages>26-35</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>29293096</pmid><doi>10.1172/JCI93555</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aging Animals Arthritis Biomedical research Cancer Collagen Connective tissue Dermis Dermis - metabolism Dermis - pathology Disease Epigenesis, Genetic Epigenetic inheritance Epigenetics Extracellular matrix Fibroblasts Fibroblasts - classification Fibroblasts - metabolism Fibroblasts - pathology Gene expression Gene Expression Regulation, Neoplastic Humans Review Series Rodents Skin Skin Neoplasms - classification Skin Neoplasms - metabolism Skin Neoplasms - pathology Specialization Therapeutic applications Transcription Transcription, Genetic Wound healing |
title | Fibroblast heterogeneity: implications for human disease |
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