Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation
Abstract Epicardium, the most outer mesothelium, exerts crucial functions in fetal heart development and adult heart regeneration. Here we use a three-step manipulation of WNT signalling entwined with BMP and RA signalling for generating a self-organized epicardial organoid that highly express with...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-024-01339-w |
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| author | Fanwen Wang Xinle Zou Huilin Zheng Tianci Kong Duanqing Pei |
| author_facet | Fanwen Wang Xinle Zou Huilin Zheng Tianci Kong Duanqing Pei |
| author_sort | Fanwen Wang |
| collection | DOAJ |
| description | Abstract Epicardium, the most outer mesothelium, exerts crucial functions in fetal heart development and adult heart regeneration. Here we use a three-step manipulation of WNT signalling entwined with BMP and RA signalling for generating a self-organized epicardial organoid that highly express with epicardium makers WT1 and TCF21 from human embryonic stem cells. After 8-days treatment of TGF-beta following by bFGF, cells enter into epithelium-mesenchymal transition and give rise to smooth muscle cells. Epicardium could also integrate and invade into mouse heart with SNAI1 expression, and give birth to numerous cardiomyocyte-like cells. Single-cell RNA seq unveils the heterogeneity and multipotency exhibited by epicardium-derived-cells and fetal-like epicardium. Meanwhile, extracellular matrix and growth factors secreted by epicardial organoid mimics the ecology of subepicardial space between the epicardium and cardiomyocytes. As such, this epicardial organoid offers a unique ground for investigating and exploring the potential of epicardium in heart development and regeneration. |
| format | Article |
| id | doaj-art-a30f7eae45734204af777a444d169cc0 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-a30f7eae45734204af777a444d169cc02025-01-19T12:40:18ZengBMCCell & Bioscience2045-37012025-01-0115111510.1186/s13578-024-01339-wHuman epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiationFanwen Wang0Xinle Zou1Huilin Zheng2Tianci Kong3Duanqing Pei4College of Life Sciences, Zhejiang UniversityLaboratory of Cell Fate Control, School of Life Sciences, Westlake UniversityLaboratory of Cell Fate Control, School of Life Sciences, Westlake UniversityCollege of Biological & Chemical Engineering, Zhejiang University of Science and TechnologyLaboratory of Cell Fate Control, School of Life Sciences, Westlake UniversityAbstract Epicardium, the most outer mesothelium, exerts crucial functions in fetal heart development and adult heart regeneration. Here we use a three-step manipulation of WNT signalling entwined with BMP and RA signalling for generating a self-organized epicardial organoid that highly express with epicardium makers WT1 and TCF21 from human embryonic stem cells. After 8-days treatment of TGF-beta following by bFGF, cells enter into epithelium-mesenchymal transition and give rise to smooth muscle cells. Epicardium could also integrate and invade into mouse heart with SNAI1 expression, and give birth to numerous cardiomyocyte-like cells. Single-cell RNA seq unveils the heterogeneity and multipotency exhibited by epicardium-derived-cells and fetal-like epicardium. Meanwhile, extracellular matrix and growth factors secreted by epicardial organoid mimics the ecology of subepicardial space between the epicardium and cardiomyocytes. As such, this epicardial organoid offers a unique ground for investigating and exploring the potential of epicardium in heart development and regeneration.https://doi.org/10.1186/s13578-024-01339-wEpicardial organoidEpithelial-mesenchymal transitionHeterogeneityParacrineEpicardial-derived cells |
| spellingShingle | Fanwen Wang Xinle Zou Huilin Zheng Tianci Kong Duanqing Pei Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation Cell & Bioscience Epicardial organoid Epithelial-mesenchymal transition Heterogeneity Paracrine Epicardial-derived cells |
| title | Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation |
| title_full | Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation |
| title_fullStr | Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation |
| title_full_unstemmed | Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation |
| title_short | Human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte- transdifferentiation |
| title_sort | human epicardial organoids from pluripotent stem cells resemble fetal stage with potential cardiomyocyte transdifferentiation |
| topic | Epicardial organoid Epithelial-mesenchymal transition Heterogeneity Paracrine Epicardial-derived cells |
| url | https://doi.org/10.1186/s13578-024-01339-w |
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