Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells
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
Affiliations
Nicole Prodan
Department 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
Faheem Ershad
Department of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USA
Arfaxad Reyes-Alcaraz
Department 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
Luge Li
Department of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA
Brandon Mistretta
Department 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, USA
Lei Gonzalez
Department of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USA
Zhoulyu Rao
Department of Mechanical Engineering, Cullen College of Engineering, University of Houston, Houston, TX 77204, USA
Cunjiang Yu
Department 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, USA
Preethi H. Gunaratne
Department 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, USA
Na Li
Department of Medicine (Section of Cardiovascular Research), Baylor College of Medicine, Houston, TX 77030, USA; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA
Robert J. Schwartz
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
Bradley K. McConnell
Department 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 author
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.
