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bioRxiv · 10.1101/2022.10.29.514354

Purkinje cardiomyocytes of the ventricular conduction system are highly diploid but not regenerative

Watanabe, H.·Tao, G.·Gan, P.·Westbury, B. C.·Cox, K. D.·Tjen, K.·Song, R.·Fishman, G. I.·Makita, T.·Sucov, H. M.
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Abstract

Inefficiency of regeneration underlies many of the pathologies associated with heart injury and disease. Ventricular diploid cardiomyocytes (CMs) are a candidate population that may have enhanced proliferative and regenerative properties [1-3], but subpopulations of diploid CMs and their regenerative capacities are not yet known. Here, using the expression marker Cntn2-GFP and the lineage marker Etv1CreERT2, we demonstrate that peripheral ventricular conduction CMs (Purkinje CMs) are disproportionately diploid (35%, vs. 4% of bulk ventricular CMs). However, this lineage had no enhanced competence to support regeneration after adult infarction. Furthermore, the CM-specific kinase Tnni3k, which strongly influences bulk ventricular CM ploidy [3] and is also associated with conduction system defects [4], had no influence on the ploidy or organization of the ventricular conduction system. Unlike the bulk diploid CM population, a significant fraction of conduction CMs remain diploid by avoiding neonatal cell cycle activity, likely contributing to these properties.

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Watanabe, H., Tao, G., Gan, P., Westbury, B. C., Cox, K. D., Tjen, K., Song, R., Fishman, G. I., Makita, T., Sucov, H. M.. 2022-10-31. Purkinje cardiomyocytes of the ventricular conduction system are highly diploid but not regenerative. https://doi.org/10.1101/2022.10.29.514354

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