TAp63 Is Important for Cardiac Differentiation of Embryonic Stem Cells and Heart Development
p63, a member of the p53 family, is essential for skin morphogenesis and epithelial stem cell maintenance. Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabecula...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2011-11, Vol.29 (11), p.1672-1683 |
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| creator | Rouleau, Matthieu Medawar, Alain Hamon, Laurent Shivtiel, Shoham Wolchinsky, Zohar Zhou, Huiqing De Rosa, Laura Candi, Eleonora de la Forest Divonne, Stéphanie Mikkola, Marja L. van Bokhoven, Hans Missero, Caterina Melino, Gerry Pucéat, Michel Aberdam, Daniel |
| description | p63, a member of the p53 family, is essential for skin morphogenesis and epithelial stem cell maintenance. Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabeculation and abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, and reduction in spontaneous calcium spikes. By the use of embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by endodermal cells. Coculture of p63‐knockdown ESCs with wild‐type ESCs, supplementation with Activin A, or overexpression of GATA‐6 rescue cardiogenesis. Therefore, TAp63 acts in a non‐cell‐autonomous manner by modulating expression of endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis that could be related to human heart disease. STEM CELLS 2011;29:1672–1683 |
| doi_str_mv | 10.1002/stem.723 |
| format | Article |
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Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabeculation and abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, and reduction in spontaneous calcium spikes. By the use of embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by endodermal cells. Coculture of p63‐knockdown ESCs with wild‐type ESCs, supplementation with Activin A, or overexpression of GATA‐6 rescue cardiogenesis. Therefore, TAp63 acts in a non‐cell‐autonomous manner by modulating expression of endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis that could be related to human heart disease. 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Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabeculation and abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, and reduction in spontaneous calcium spikes. By the use of embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by endodermal cells. Coculture of p63‐knockdown ESCs with wild‐type ESCs, supplementation with Activin A, or overexpression of GATA‐6 rescue cardiogenesis. Therefore, TAp63 acts in a non‐cell‐autonomous manner by modulating expression of endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis that could be related to human heart disease. STEM CELLS 2011;29:1672–1683</description><subject>Animals</subject><subject>Cardiogenesis</subject><subject>Cardiomyopathy</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Line</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Embryonic Stem Cells - ultrastructure</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>GATA</subject><subject>GATA6 Transcription Factor - genetics</subject><subject>GATA6 Transcription Factor - metabolism</subject><subject>Heart - embryology</subject><subject>Heart - growth & development</subject><subject>HMGB Proteins - genetics</subject><subject>HMGB Proteins - metabolism</subject><subject>Immunoblotting</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microscopy, Electron, Transmission</subject><subject>p63</subject><subject>Phosphoproteins - genetics</subject><subject>Phosphoproteins - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>sox17</subject><subject>SOXF Transcription Factors - genetics</subject><subject>SOXF Transcription Factors - metabolism</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>trp63</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1Lw0AQQBdRbK2Cv0D26CV1NptNd48lrbZQ8dB6E8J-QiTJht2o9N-bUPXmaebw5g08hG4JzAlA-hB728wXKT1DU8IykWSC8PNhhzxPGAgxQVcxvgOQjHF-iSYp4YLnAqbo7bDscoq3EW-bzodetj12PuBCBlNJjVeVczbYtq9kX_kWe4fXjQpH31Ya74e3uLB1HbFsDd5YGXq8sp-29l0z3FyjCyfraG9-5gy9Pq4PxSbZvTxti-Uu0ZRzmmSGqAWhQiqgxCxSDtRJ7gxnKTVAiFCOgDKQQ-oUp0JnjFGm2QBLoZWgM3R_8urgYwzWlV2oGhmOJYFyDFSOgcoh0IDendDuQzXW_IG_RQYgOQFfVW2P_4rK_WH9PAq_AQqDbzE</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Rouleau, Matthieu</creator><creator>Medawar, Alain</creator><creator>Hamon, Laurent</creator><creator>Shivtiel, Shoham</creator><creator>Wolchinsky, Zohar</creator><creator>Zhou, Huiqing</creator><creator>De Rosa, Laura</creator><creator>Candi, Eleonora</creator><creator>de la Forest Divonne, Stéphanie</creator><creator>Mikkola, Marja L.</creator><creator>van Bokhoven, Hans</creator><creator>Missero, Caterina</creator><creator>Melino, Gerry</creator><creator>Pucéat, Michel</creator><creator>Aberdam, Daniel</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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></search><sort><creationdate>201111</creationdate><title>TAp63 Is Important for Cardiac Differentiation of Embryonic Stem Cells and Heart Development</title><author>Rouleau, Matthieu ; 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Here, we report an unexpected role of TAp63 in cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac development, including dilation of both ventricles, a defect in trabeculation and abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial disorganization, and reduction in spontaneous calcium spikes. By the use of embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by endodermal cells. Coculture of p63‐knockdown ESCs with wild‐type ESCs, supplementation with Activin A, or overexpression of GATA‐6 rescue cardiogenesis. Therefore, TAp63 acts in a non‐cell‐autonomous manner by modulating expression of endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis that could be related to human heart disease. STEM CELLS 2011;29:1672–1683</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21898690</pmid><doi>10.1002/stem.723</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Stem cells (Dayton, Ohio), 2011-11, Vol.29 (11), p.1672-1683 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Cardiogenesis Cardiomyopathy Cell Differentiation - genetics Cell Differentiation - physiology Cell Line Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Embryonic Stem Cells - ultrastructure Flow Cytometry Fluorescent Antibody Technique GATA GATA6 Transcription Factor - genetics GATA6 Transcription Factor - metabolism Heart - embryology Heart - growth & development HMGB Proteins - genetics HMGB Proteins - metabolism Immunoblotting Mice Mice, Knockout Microscopy, Electron, Transmission p63 Phosphoproteins - genetics Phosphoproteins - metabolism Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction sox17 SOXF Transcription Factors - genetics SOXF Transcription Factors - metabolism Trans-Activators - genetics Trans-Activators - metabolism trp63 |
| title | TAp63 Is Important for Cardiac Differentiation of Embryonic Stem Cells and Heart Development |
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