CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells
Abstract The epicardium is a mesothelial layer covering the myocardium serving as a progenitor source during cardiac development. The epicardium reactivates upon cardiac injury supporting cardiac repair and regeneration. Fine-tuned balanced signaling regulates cell plasticity and cell-fate decisions...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-02-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-022-00207-w |
| _version_ | 1798023840934133760 |
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| author | Julia Junghof Yuta Kogure Tian Yu Eva María Verdugo-Sivianes Megumi Narita Antonio Lucena-Cacace Yoshinori Yoshida |
| author_facet | Julia Junghof Yuta Kogure Tian Yu Eva María Verdugo-Sivianes Megumi Narita Antonio Lucena-Cacace Yoshinori Yoshida |
| author_sort | Julia Junghof |
| collection | DOAJ |
| description | Abstract The epicardium is a mesothelial layer covering the myocardium serving as a progenitor source during cardiac development. The epicardium reactivates upon cardiac injury supporting cardiac repair and regeneration. Fine-tuned balanced signaling regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) via epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a biomarker defining lineage specification in human active epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results highlight the importance of tracing CDH18 expression in hiPSC-derived epicardial cells, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine. |
| first_indexed | 2024-04-11T17:53:03Z |
| format | Article |
| id | doaj.art-40516e69d4954444b0f3718e97fb0f06 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-04-11T17:53:03Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-40516e69d4954444b0f3718e97fb0f062022-12-22T04:10:59ZengNature Portfolionpj Regenerative Medicine2057-39952022-02-017111410.1038/s41536-022-00207-wCDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cellsJulia Junghof0Yuta Kogure1Tian Yu2Eva María Verdugo-Sivianes3Megumi Narita4Antonio Lucena-Cacace5Yoshinori Yoshida6Center for iPS Cell Research and Application, Kyoto UniversityCenter for iPS Cell Research and Application, Kyoto UniversityCenter for iPS Cell Research and Application, Kyoto UniversityInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones CientíficasCenter for iPS Cell Research and Application, Kyoto UniversityCenter for iPS Cell Research and Application, Kyoto UniversityCenter for iPS Cell Research and Application, Kyoto UniversityAbstract The epicardium is a mesothelial layer covering the myocardium serving as a progenitor source during cardiac development. The epicardium reactivates upon cardiac injury supporting cardiac repair and regeneration. Fine-tuned balanced signaling regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) via epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a biomarker defining lineage specification in human active epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results highlight the importance of tracing CDH18 expression in hiPSC-derived epicardial cells, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine.https://doi.org/10.1038/s41536-022-00207-w |
| spellingShingle | Julia Junghof Yuta Kogure Tian Yu Eva María Verdugo-Sivianes Megumi Narita Antonio Lucena-Cacace Yoshinori Yoshida CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells npj Regenerative Medicine |
| title | CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells |
| title_full | CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells |
| title_fullStr | CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells |
| title_full_unstemmed | CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells |
| title_short | CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells |
| title_sort | cdh18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells |
| url | https://doi.org/10.1038/s41536-022-00207-w |
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