A novel cardiomyogenic role for Isl1+ neural crest cells in the inflow tract

Konstantinos E. Hatzistergos, Michael A. Durante, Krystalenia Valasaki, Amarylis C.B.A. Wanschel, J. William Harbour, Joshua M. Hare

Research output: Contribution to journalArticlepeer-review

Abstract

The degree to which populations of cardiac progenitors (CPCs) persist in the postnatal heart remains a controversial issue in cardiobiology. To address this question, we conducted a spatiotemporally resolved analysis of CPC deployment dynamics, tracking cells expressing the pan-CPC gene Isl1. Most CPCs undergo programmed silencing during early cardiogenesis through proteasome-mediated and PRC2 (Polycomb group repressive complex 2)–mediated Isl1 repression, selectively in the outflow tract. A notable exception is a domain of cardiac neural crest cells (CNCs) in the inflow tract. These “dorsal CNCs” are regulated through a Wnt/β-catenin/Isl1 feedback loop and generate a limited number of trabecular cardiomyocytes that undergo multiple clonal divisions during compaction, to eventually produce ~10% of the biventricular myocardium. After birth, CNCs continue to generate cardiomyocytes that, however, exhibit diminished clonal amplification dynamics. Thus, although the postnatal heart sustains cardiomyocyte-producing CNCs, their regenerative potential is likely diminished by the loss of trabeculation-like proliferative properties.

Original languageEnglish (US)
Article numbereaba9950
JournalScience Advances
Volume6
Issue number49
DOIs
StatePublished - Dec 2 2020

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'A novel cardiomyogenic role for Isl1<sup>+</sup> neural crest cells in the inflow tract'. Together they form a unique fingerprint.

Cite this