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Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration
The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing...
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| Published in: | Nature communications 2022-12, Vol.13 (1), p.7704-18, Article 7704 |
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| creator | Xia, Yu Duca, Sierra Perder, Björn Dündar, Friederike Zumbo, Paul Qiu, Miaoyan Yao, Jun Cao, Yingxi Harrison, Michael R. M. Zangi, Lior Betel, Doron Cao, Jingli |
| description | The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we define the epithelial and mesenchymal subsets of the epicardium. We further identify a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by
ptx3a
and
col12a1b
expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and
pdgfra
+
hapln1a
+
mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reduced
nrg1
expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
The epicardium supports heart regeneration, though precisely how is unclear. Here the authors define an activated epicardial progenitor population as the source of essential cell types and paracrine factors for successful heart regeneration in zebrafish. |
| doi_str_mv | 10.1038/s41467-022-35433-9 |
| format | article |
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ptx3a
and
col12a1b
expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and
pdgfra
+
hapln1a
+
mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reduced
nrg1
expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
The epicardium supports heart regeneration, though precisely how is unclear. Here the authors define an activated epicardial progenitor population as the source of essential cell types and paracrine factors for successful heart regeneration in zebrafish.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/s41467-022-35433-9</identifier><identifier>PMID: 36513650</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 14/19 ; 14/32 ; 38 ; 38/32 ; 45/41 ; 45/91 ; 631/136/142 ; 631/443/592/2725 ; 631/443/592/2726 ; 631/532/489 ; 64/116 ; Ablation ; Animals ; Cell differentiation ; Cell number ; Cells (biology) ; Danio rerio ; Epicardium ; Epithelial-Mesenchymal Transition - genetics ; Extracellular Matrix Proteins - metabolism ; Gene sequencing ; Heart ; Heart - physiology ; Heart Injuries - genetics ; Humanities and Social Sciences ; Mesenchyme ; multidisciplinary ; Paracrine signalling ; Pericardium ; Progenitor cells ; Proteoglycans - metabolism ; Regeneration ; Science ; Science (multidisciplinary) ; Stem cells ; Stem Cells - metabolism ; Vertebrates ; Zebrafish ; Zebrafish - metabolism ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism</subject><ispartof>Nature communications, 2022-12, Vol.13 (1), p.7704-18, Article 7704</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-2f7a4122c4c24469f29289d363a79ccd72c8e12d4ca794eabfdc567156018faf3</citedby><cites>FETCH-LOGICAL-c540t-2f7a4122c4c24469f29289d363a79ccd72c8e12d4ca794eabfdc567156018faf3</cites><orcidid>0000-0002-2301-112X ; 0000-0002-8006-7752 ; 0000-0003-1703-9879 ; 0000-0001-5938-6604</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2753902767/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2753902767?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36513650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xia, Yu</creatorcontrib><creatorcontrib>Duca, Sierra</creatorcontrib><creatorcontrib>Perder, Björn</creatorcontrib><creatorcontrib>Dündar, Friederike</creatorcontrib><creatorcontrib>Zumbo, Paul</creatorcontrib><creatorcontrib>Qiu, Miaoyan</creatorcontrib><creatorcontrib>Yao, Jun</creatorcontrib><creatorcontrib>Cao, Yingxi</creatorcontrib><creatorcontrib>Harrison, Michael R. M.</creatorcontrib><creatorcontrib>Zangi, Lior</creatorcontrib><creatorcontrib>Betel, Doron</creatorcontrib><creatorcontrib>Cao, Jingli</creatorcontrib><title>Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we define the epithelial and mesenchymal subsets of the epicardium. We further identify a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by
ptx3a
and
col12a1b
expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and
pdgfra
+
hapln1a
+
mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reduced
nrg1
expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
The epicardium supports heart regeneration, though precisely how is unclear. Here the authors define an activated epicardial progenitor population as the source of essential cell types and paracrine factors for successful heart regeneration in zebrafish.</description><subject>13/51</subject><subject>14/19</subject><subject>14/32</subject><subject>38</subject><subject>38/32</subject><subject>45/41</subject><subject>45/91</subject><subject>631/136/142</subject><subject>631/443/592/2725</subject><subject>631/443/592/2726</subject><subject>631/532/489</subject><subject>64/116</subject><subject>Ablation</subject><subject>Animals</subject><subject>Cell differentiation</subject><subject>Cell number</subject><subject>Cells (biology)</subject><subject>Danio rerio</subject><subject>Epicardium</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Gene sequencing</subject><subject>Heart</subject><subject>Heart - physiology</subject><subject>Heart Injuries - genetics</subject><subject>Humanities and Social Sciences</subject><subject>Mesenchyme</subject><subject>multidisciplinary</subject><subject>Paracrine signalling</subject><subject>Pericardium</subject><subject>Progenitor cells</subject><subject>Proteoglycans - metabolism</subject><subject>Regeneration</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Vertebrates</subject><subject>Zebrafish</subject><subject>Zebrafish - metabolism</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1rFDEYxgdRbKn9BzxIwIuXqfmcTC5CKWoLBS96Du9m3uxmmZ1sk0xB_3qzO7W2HgyEfLxPfnkSnqZ5y-gFo6L_mCWTnW4p561QUojWvGhOOZWsZZqLl0_mJ815zltamzCsl_J1cyI6xWqnp024dCXcQwlxItETICXBlANOhexTXOMUSkwkFyhIwkTKBgnug4M0hHlHQiYJ7-aQcCC-6n7hKoEPeUM2CKnUYiVgOuLfNK88jBnPH8az5seXz9-vrtvbb19vri5vW6ckLS33GiTj3EnHpeyM54b3ZhCdAG2cGzR3PTI-SFfXEmHlB6c6zVRHWe_Bi7PmZuEOEbZ2n8IO0k8bIdjjRkxrW60FN6IVgJ1kxnSOeslcD6g6hUb2DnpgoCvr08Laz6sdDq5-S4LxGfR5ZQobu4731mipNTMV8OEBkOLdjLnYXcgOxxEmjHO2XCupqGC9qtL3_0i3cU5T_aqDShjKdXdwxBeVSzHnhP7RDKP2EAy7BMPWYNhjMOzBxbunz3g88icGVSAWQa6laY3p793_wf4GmjnE9w</recordid><startdate>20221213</startdate><enddate>20221213</enddate><creator>Xia, Yu</creator><creator>Duca, Sierra</creator><creator>Perder, Björn</creator><creator>Dündar, Friederike</creator><creator>Zumbo, Paul</creator><creator>Qiu, Miaoyan</creator><creator>Yao, Jun</creator><creator>Cao, Yingxi</creator><creator>Harrison, Michael R. 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M. ; Zangi, Lior ; Betel, Doron ; Cao, Jingli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-2f7a4122c4c24469f29289d363a79ccd72c8e12d4ca794eabfdc567156018faf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>13/51</topic><topic>14/19</topic><topic>14/32</topic><topic>38</topic><topic>38/32</topic><topic>45/41</topic><topic>45/91</topic><topic>631/136/142</topic><topic>631/443/592/2725</topic><topic>631/443/592/2726</topic><topic>631/532/489</topic><topic>64/116</topic><topic>Ablation</topic><topic>Animals</topic><topic>Cell differentiation</topic><topic>Cell number</topic><topic>Cells (biology)</topic><topic>Danio rerio</topic><topic>Epicardium</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Gene sequencing</topic><topic>Heart</topic><topic>Heart - physiology</topic><topic>Heart Injuries - genetics</topic><topic>Humanities and Social Sciences</topic><topic>Mesenchyme</topic><topic>multidisciplinary</topic><topic>Paracrine signalling</topic><topic>Pericardium</topic><topic>Progenitor cells</topic><topic>Proteoglycans - metabolism</topic><topic>Regeneration</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Vertebrates</topic><topic>Zebrafish</topic><topic>Zebrafish - metabolism</topic><topic>Zebrafish Proteins - genetics</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xia, Yu</creatorcontrib><creatorcontrib>Duca, Sierra</creatorcontrib><creatorcontrib>Perder, Björn</creatorcontrib><creatorcontrib>Dündar, Friederike</creatorcontrib><creatorcontrib>Zumbo, Paul</creatorcontrib><creatorcontrib>Qiu, Miaoyan</creatorcontrib><creatorcontrib>Yao, Jun</creatorcontrib><creatorcontrib>Cao, Yingxi</creatorcontrib><creatorcontrib>Harrison, Michael R. 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M.</au><au>Zangi, Lior</au><au>Betel, Doron</au><au>Cao, Jingli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2022-12-13</date><risdate>2022</risdate><volume>13</volume><issue>1</issue><spage>7704</spage><epage>18</epage><pages>7704-18</pages><artnum>7704</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we define the epithelial and mesenchymal subsets of the epicardium. We further identify a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by
ptx3a
and
col12a1b
expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and
pdgfra
+
hapln1a
+
mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocks heart regeneration through reduced
nrg1
expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
The epicardium supports heart regeneration, though precisely how is unclear. Here the authors define an activated epicardial progenitor population as the source of essential cell types and paracrine factors for successful heart regeneration in zebrafish.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36513650</pmid><doi>10.1038/s41467-022-35433-9</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-2301-112X</orcidid><orcidid>https://orcid.org/0000-0002-8006-7752</orcidid><orcidid>https://orcid.org/0000-0003-1703-9879</orcidid><orcidid>https://orcid.org/0000-0001-5938-6604</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-1723 |
| ispartof | Nature communications, 2022-12, Vol.13 (1), p.7704-18, Article 7704 |
| issn | 2041-1723 2041-1723 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_3ae641996c0f41c8ae565e948ca8a1a7 |
| source | Publicly Available Content Database; Nature; PubMed Central; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 13/51 14/19 14/32 38 38/32 45/41 45/91 631/136/142 631/443/592/2725 631/443/592/2726 631/532/489 64/116 Ablation Animals Cell differentiation Cell number Cells (biology) Danio rerio Epicardium Epithelial-Mesenchymal Transition - genetics Extracellular Matrix Proteins - metabolism Gene sequencing Heart Heart - physiology Heart Injuries - genetics Humanities and Social Sciences Mesenchyme multidisciplinary Paracrine signalling Pericardium Progenitor cells Proteoglycans - metabolism Regeneration Science Science (multidisciplinary) Stem cells Stem Cells - metabolism Vertebrates Zebrafish Zebrafish - metabolism Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration |
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