Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells

• Published in: iScience 2022-11, Vol.25 (11), p.105402-105402, Article 105402
• Main Authors: Prodan, Nicole, Ershad, Faheem, Reyes-Alcaraz, Arfaxad, Li, Luge, Mistretta, Brandon, Gonzalez, Lei, Rao, Zhoulyu, Yu, Cunjiang, Gunaratne, Preethi H., Li, Na, Schwartz, Robert J., McConnell, Bradley K.
• Format: Article
• Language: English
• Subjects: Bioengineering; Cell biology; Stem cells research
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105402

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. [Display omitted] •Small molecule treatment of human cardiomyocytes leads to Purkinje differentiation•Small molecule differentiation results in key Purkinje gene expression•Differentiated Purkinje cells can conduct fast electrical signals•Differentiated Purkinje cells are comparable to native Purkinje cells Bioengineering; Cell biology; Stem cells research