Direct Reprogramming of Cardiomyocytes Into Cardiac Purkinje-Like Cells

Authors

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

Publication Date

11-18-2022

Journal

iScience

DOI

10.1016/j.isci.2022.105402

PMID

36388958

PMCID

PMC9646947

PubMedCentral® Posted Date

10-20-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Bioengineering, Cell biology, Stem cells research

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

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