Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation
Our understanding of signaling pathways regulating the cell fate of human embryonic stem cells (hESCs) is limited. Calcineurin‐NFAT signaling is associated with a wide range of biological processes and diseases. However, its role in controlling hESC fate remains unclear. Here, we report that calcine...
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| Veröffentlicht in: | Journal of cellular physiology 2021-08, Vol.236 (8), p.5698-5714 |
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| creator | Chen, Hao Zeng, Yanwu Shao, Min Zhao, Hanzhi Fang, Zhuoqing Gu, Junjie Liao, Bing Jin, Ying |
| description | Our understanding of signaling pathways regulating the cell fate of human embryonic stem cells (hESCs) is limited. Calcineurin‐NFAT signaling is associated with a wide range of biological processes and diseases. However, its role in controlling hESC fate remains unclear. Here, we report that calcineurin A gamma and the NFATc3/SRPX2 axis control the expression of lineage and epithelial–mesenchymal transition (EMT) markers in hESCs. Knockdown of PPP3CC, the gene encoding calcineurin A gamma, or NFATC3, downregulates certain markers both at the self‐renewal state and during differentiation of hESCs. Furthermore, NFATc3 interacts with c‐JUN and regulates the expression of SRPX2, the gene encoding a secreted glycoprotein known as a ligand of uPAR. We show that SRPX2 is a downstream target of NFATc3. Both SRPX2 and uPAR participate in controlling expression of lineage and EMT markers. Importantly, SRPX2 knockdown diminishes the upregulation of multiple lineage and EMT markers induced by co‐overexpression of NFATc3 and c‐JUN in hESCs. Together, this study uncovers a previously unknown role of calcineurin A gamma and the NFATc3/SRPX2 axis in modulating the fate determination of hESCs. |
| doi_str_mv | 10.1002/jcp.30255 |
| format | Article |
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Calcineurin‐NFAT signaling is associated with a wide range of biological processes and diseases. However, its role in controlling hESC fate remains unclear. Here, we report that calcineurin A gamma and the NFATc3/SRPX2 axis control the expression of lineage and epithelial–mesenchymal transition (EMT) markers in hESCs. Knockdown of PPP3CC, the gene encoding calcineurin A gamma, or NFATC3, downregulates certain markers both at the self‐renewal state and during differentiation of hESCs. Furthermore, NFATc3 interacts with c‐JUN and regulates the expression of SRPX2, the gene encoding a secreted glycoprotein known as a ligand of uPAR. We show that SRPX2 is a downstream target of NFATc3. Both SRPX2 and uPAR participate in controlling expression of lineage and EMT markers. Importantly, SRPX2 knockdown diminishes the upregulation of multiple lineage and EMT markers induced by co‐overexpression of NFATc3 and c‐JUN in hESCs. Together, this study uncovers a previously unknown role of calcineurin A gamma and the NFATc3/SRPX2 axis in modulating the fate determination of hESCs.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.30255</identifier><identifier>PMID: 33393109</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Biological activity ; Biomarkers ; Calcineurin ; calcineurin A gamma ; Cell differentiation ; Cell fate ; Cell self-renewal ; Differentiation (biology) ; Embryo cells ; Gene expression ; Glycoproteins ; hESC differentiation ; Mesenchyme ; NF-AT protein ; NFATc3 ; Signaling ; SRPX2 ; Stem cells ; uPAR</subject><ispartof>Journal of cellular physiology, 2021-08, Vol.236 (8), p.5698-5714</ispartof><rights>2020 Wiley Periodicals LLC</rights><rights>2020 Wiley Periodicals LLC.</rights><rights>2021 Wiley Periodicals LLC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-f93d3fe3af374cfa86160244619a875615a82bebc808454c4a4deee93b5f6f863</citedby><cites>FETCH-LOGICAL-c3535-f93d3fe3af374cfa86160244619a875615a82bebc808454c4a4deee93b5f6f863</cites><orcidid>0000-0003-0070-2048</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.30255$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.30255$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33393109$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hao</creatorcontrib><creatorcontrib>Zeng, Yanwu</creatorcontrib><creatorcontrib>Shao, Min</creatorcontrib><creatorcontrib>Zhao, Hanzhi</creatorcontrib><creatorcontrib>Fang, Zhuoqing</creatorcontrib><creatorcontrib>Gu, Junjie</creatorcontrib><creatorcontrib>Liao, Bing</creatorcontrib><creatorcontrib>Jin, Ying</creatorcontrib><title>Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Our understanding of signaling pathways regulating the cell fate of human embryonic stem cells (hESCs) is limited. Calcineurin‐NFAT signaling is associated with a wide range of biological processes and diseases. However, its role in controlling hESC fate remains unclear. Here, we report that calcineurin A gamma and the NFATc3/SRPX2 axis control the expression of lineage and epithelial–mesenchymal transition (EMT) markers in hESCs. Knockdown of PPP3CC, the gene encoding calcineurin A gamma, or NFATC3, downregulates certain markers both at the self‐renewal state and during differentiation of hESCs. Furthermore, NFATc3 interacts with c‐JUN and regulates the expression of SRPX2, the gene encoding a secreted glycoprotein known as a ligand of uPAR. We show that SRPX2 is a downstream target of NFATc3. Both SRPX2 and uPAR participate in controlling expression of lineage and EMT markers. Importantly, SRPX2 knockdown diminishes the upregulation of multiple lineage and EMT markers induced by co‐overexpression of NFATc3 and c‐JUN in hESCs. Together, this study uncovers a previously unknown role of calcineurin A gamma and the NFATc3/SRPX2 axis in modulating the fate determination of hESCs.</description><subject>Biological activity</subject><subject>Biomarkers</subject><subject>Calcineurin</subject><subject>calcineurin A gamma</subject><subject>Cell differentiation</subject><subject>Cell fate</subject><subject>Cell self-renewal</subject><subject>Differentiation (biology)</subject><subject>Embryo cells</subject><subject>Gene expression</subject><subject>Glycoproteins</subject><subject>hESC differentiation</subject><subject>Mesenchyme</subject><subject>NF-AT protein</subject><subject>NFATc3</subject><subject>Signaling</subject><subject>SRPX2</subject><subject>Stem cells</subject><subject>uPAR</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp10M1O3DAUBWCrKipTyoIXqCx1Qxdh_JvYy9EIWhACVEBiZznONfUocQY7EczbExhgUamru7ifjo4OQgeUHFFC2Hzl1kecMCk_oRkluipEKdlnNJt-tNBS0F30NecVIURrzr-gXc655pOcIbu0rQsRxhQiXuB723UW29jgi5PFjePz6z9Xdwzbp5Cx6-OQQj0OgIce_x07GzF0ddr0MTicB-iwg7bFTfAeEsQh2CH08Rva8bbNsP9299DtyfHN8ndxfvnrdLk4LxyXXBZe84Z74NbzSjhvVUlLwoQoqbaqkiWVVrEaaqeIElI4YUUDAJrX0pdelXwPHW5z16l_GCEPpgv5pZCN0I_ZMFFJopTWdKI__qGrfkxxameYZJVSpZRkUj-3yqU-5wTerFPobNoYSszL7mba3bzuPtnvb4lj3UHzId-HnsB8Cx5DC5v_J5mz5dU28hl1FYrI</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Chen, Hao</creator><creator>Zeng, Yanwu</creator><creator>Shao, Min</creator><creator>Zhao, Hanzhi</creator><creator>Fang, Zhuoqing</creator><creator>Gu, Junjie</creator><creator>Liao, Bing</creator><creator>Jin, Ying</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0070-2048</orcidid></search><sort><creationdate>202108</creationdate><title>Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation</title><author>Chen, Hao ; Zeng, Yanwu ; Shao, Min ; Zhao, Hanzhi ; Fang, Zhuoqing ; Gu, Junjie ; Liao, Bing ; Jin, Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3535-f93d3fe3af374cfa86160244619a875615a82bebc808454c4a4deee93b5f6f863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biological activity</topic><topic>Biomarkers</topic><topic>Calcineurin</topic><topic>calcineurin A gamma</topic><topic>Cell differentiation</topic><topic>Cell fate</topic><topic>Cell self-renewal</topic><topic>Differentiation (biology)</topic><topic>Embryo cells</topic><topic>Gene expression</topic><topic>Glycoproteins</topic><topic>hESC differentiation</topic><topic>Mesenchyme</topic><topic>NF-AT protein</topic><topic>NFATc3</topic><topic>Signaling</topic><topic>SRPX2</topic><topic>Stem cells</topic><topic>uPAR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hao</creatorcontrib><creatorcontrib>Zeng, Yanwu</creatorcontrib><creatorcontrib>Shao, Min</creatorcontrib><creatorcontrib>Zhao, Hanzhi</creatorcontrib><creatorcontrib>Fang, Zhuoqing</creatorcontrib><creatorcontrib>Gu, Junjie</creatorcontrib><creatorcontrib>Liao, Bing</creatorcontrib><creatorcontrib>Jin, Ying</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Hao</au><au>Zeng, Yanwu</au><au>Shao, Min</au><au>Zhao, Hanzhi</au><au>Fang, Zhuoqing</au><au>Gu, Junjie</au><au>Liao, Bing</au><au>Jin, Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2021-08</date><risdate>2021</risdate><volume>236</volume><issue>8</issue><spage>5698</spage><epage>5714</epage><pages>5698-5714</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Our understanding of signaling pathways regulating the cell fate of human embryonic stem cells (hESCs) is limited. Calcineurin‐NFAT signaling is associated with a wide range of biological processes and diseases. However, its role in controlling hESC fate remains unclear. Here, we report that calcineurin A gamma and the NFATc3/SRPX2 axis control the expression of lineage and epithelial–mesenchymal transition (EMT) markers in hESCs. Knockdown of PPP3CC, the gene encoding calcineurin A gamma, or NFATC3, downregulates certain markers both at the self‐renewal state and during differentiation of hESCs. Furthermore, NFATc3 interacts with c‐JUN and regulates the expression of SRPX2, the gene encoding a secreted glycoprotein known as a ligand of uPAR. We show that SRPX2 is a downstream target of NFATc3. Both SRPX2 and uPAR participate in controlling expression of lineage and EMT markers. Importantly, SRPX2 knockdown diminishes the upregulation of multiple lineage and EMT markers induced by co‐overexpression of NFATc3 and c‐JUN in hESCs. 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| subjects | Biological activity Biomarkers Calcineurin calcineurin A gamma Cell differentiation Cell fate Cell self-renewal Differentiation (biology) Embryo cells Gene expression Glycoproteins hESC differentiation Mesenchyme NF-AT protein NFATc3 Signaling SRPX2 Stem cells uPAR |
| title | Calcineurin A gamma and NFATc3/SRPX2 axis contribute to human embryonic stem cell differentiation |
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