TY - JOUR
T1 - A novel cardiomyogenic role for Isl1+ neural crest cells in the inflow tract
AU - Hatzistergos, Konstantinos E.
AU - Durante, Michael A.
AU - Valasaki, Krystalenia
AU - Wanschel, Amarylis C.B.A.
AU - William Harbour, J.
AU - Hare, Joshua M.
N1 - Publisher Copyright:
Copyright © 2020 The Authors,
PY - 2020/12/2
Y1 - 2020/12/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097125158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097125158&partnerID=8YFLogxK
U2 - 10.1126/sciadv.aba9950
DO - 10.1126/sciadv.aba9950
M3 - Article
C2 - 33268364
AN - SCOPUS:85097125158
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 49
M1 - eaba9950
ER -