Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells
Summary: Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222016741 |
| _version_ | 1798045231877193728 |
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| author | Nicole Prodan Faheem Ershad Arfaxad Reyes-Alcaraz Luge Li Brandon Mistretta Lei Gonzalez Zhoulyu Rao Cunjiang Yu Preethi H. Gunaratne Na Li Robert J. Schwartz Bradley K. McConnell |
| author_facet | Nicole Prodan Faheem Ershad Arfaxad Reyes-Alcaraz Luge Li Brandon Mistretta Lei Gonzalez Zhoulyu Rao Cunjiang Yu Preethi H. Gunaratne Na Li Robert J. Schwartz Bradley K. McConnell |
| author_sort | Nicole Prodan |
| collection | DOAJ |
| description | Summary: Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical signals. Purkinje cells have tremendous potential as a regenerative treatment because they may intrinsically integrate with the CCS of a recipient myocardium, resulting in more efficient electrical conduction in diseased hearts. This study is the first to demonstrate an effective protocol for the direct reprogramming of human cardiomyocytes into cardiac Purkinje-like cells using small molecules. The cells generated were genetically and functionally similar to native cardiac Purkinje cells, where expression of key cardiac Purkinje genes such as CNTN2, ETV1, PCP4, IRX3, SCN5a, HCN2 and the conduction of electrical signals with increased velocity was observed. This study may help to advance the quest to finding an optimized cell therapy for heart regeneration. |
| first_indexed | 2024-04-11T23:17:36Z |
| format | Article |
| id | doaj.art-4c481036b7274d13bdf13ca5affea25f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T23:17:36Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4c481036b7274d13bdf13ca5affea25f2022-12-22T03:57:33ZengElsevieriScience2589-00422022-11-012511105402Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cellsNicole Prodan0Faheem Ershad1Arfaxad Reyes-Alcaraz2Luge Li3Brandon Mistretta4Lei Gonzalez5Zhoulyu Rao6Cunjiang Yu7Preethi H. Gunaratne8Na Li9Robert J. Schwartz10Bradley K. McConnell11Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Health-2 (H2) Building, Room 5024, Houston, TX 77204-5037, USADepartment of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USADepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Health-2 (H2) Building, Room 5024, Houston, TX 77204-5037, USADepartment of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USADepartment of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA; Department of Biology and Biochemistry, UH-Sequencing & Gene Editing Core, University of Houston, Houston, TX 77204, USADepartment of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USADepartment of Mechanical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USADepartment of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USA; Department of Mechanical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USADepartment of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA; Department of Biology and Biochemistry, UH-Sequencing & Gene Editing Core, University of Houston, Houston, TX 77204, USADepartment of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USADepartment of Biology and Biochemistry, University of Houston, Houston, TX 77204, USADepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 4349 Martin Luther King Blvd, Health-2 (H2) Building, Room 5024, Houston, TX 77204-5037, USA; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA; Corresponding authorSummary: Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical signals. Purkinje cells have tremendous potential as a regenerative treatment because they may intrinsically integrate with the CCS of a recipient myocardium, resulting in more efficient electrical conduction in diseased hearts. This study is the first to demonstrate an effective protocol for the direct reprogramming of human cardiomyocytes into cardiac Purkinje-like cells using small molecules. The cells generated were genetically and functionally similar to native cardiac Purkinje cells, where expression of key cardiac Purkinje genes such as CNTN2, ETV1, PCP4, IRX3, SCN5a, HCN2 and the conduction of electrical signals with increased velocity was observed. This study may help to advance the quest to finding an optimized cell therapy for heart regeneration.http://www.sciencedirect.com/science/article/pii/S2589004222016741BioengineeringCell biologyStem cells research |
| spellingShingle | Nicole Prodan Faheem Ershad Arfaxad Reyes-Alcaraz Luge Li Brandon Mistretta Lei Gonzalez Zhoulyu Rao Cunjiang Yu Preethi H. Gunaratne Na Li Robert J. Schwartz Bradley K. McConnell Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells iScience Bioengineering Cell biology Stem cells research |
| title | Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells |
| title_full | Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells |
| title_fullStr | Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells |
| title_full_unstemmed | Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells |
| title_short | Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells |
| title_sort | direct reprogramming of cardiomyocytes into cardiac purkinje like cells |
| topic | Bioengineering Cell biology Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222016741 |
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