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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number105402
JournaliScience
Volume25
Issue number11
DOIs
StatePublished - Nov 18 2022

All Science Journal Classification (ASJC) codes

  • General

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