LRRC10 Regulates Mammalian Cardiomyocyte Cell Cycle During Heart Regeneration

Overview

Journal NPJ Regen Med

Date 2023 Jul 28

PMID 37507410

Authors

Rebecca J Salamon

Megan C McKeon

Jiyoung Bae

Xiaoya Zhang

Wyatt G Paltzer

Kayla N Wanless

Alyssa R Schuett

Dakota J Nuttall

Stephen A Nemr

Rupa Sridharan

Youngsook Lee

Timothy J Kamp

Ahmed I Mahmoud

Affiliations

Soon will be listed here.

Abstract

Leucine-rich repeat containing 10 (LRRC10) is a cardiomyocyte-specific protein, but its role in cardiac biology is little understood. Recently Lrrc10 was identified as required for endogenous cardiac regeneration in zebrafish; however, whether LRRC10 plays a role in mammalian heart regeneration remains unclear. In this study, we demonstrate that Lrrc10 knockout mice exhibit a loss of the neonatal mouse regenerative response, marked by reduced cardiomyocyte cytokinesis and increased cardiomyocyte binucleation. Interestingly, LRRC10 deletion disrupts the regenerative transcriptional landscape of the regenerating neonatal mouse heart. Remarkably, cardiac overexpression of LRRC10 restores cardiomyocyte cytokinesis, increases cardiomyocyte mononucleation, and the cardiac regenerative capacity of Lrrc10 mice. Our results are consistent with a model in which LRRC10 is required for cardiomyocyte cytokinesis as well as regulation of the transcriptional landscape during mammalian heart regeneration.

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