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

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/?-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.

SUBMITTER: Hatzistergos KE

PROVIDER: S-EPMC7821887 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A novel cardiomyogenic role for Isl1<sup>+</sup> neural crest cells in the inflow tract.

Hatzistergos Konstantinos E KE Durante Michael A MA Valasaki Krystalenia K Wanschel Amarylis C B A ACBA Harbour J William JW Hare Joshua M JM

Science advances 20201202 49

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 <i>Isl1</i> 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. ...[more]

PMID: 33268364

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Project description:IntroductionCellular cardiomyoplasty has rapidly risen to prominence in the clinic following a myocardial infarction; however, low engraftment of transplanted cells limits the therapeutic benefit to these procedures. Recently, lineage-specific stem cells differentiated into cardiomyocytes have gained much attention to assist in the repair of an injured heart tissue; however, questions regarding the ideal cell source remain. In the present study, we have identified a source that is easy to extract stem cells from and show that the cells present have a high plasticity toward the cardiomyogenic lineage. We focused on the recently discovered neural crest stem cells residing in the periodontal ligament that can be easily obtained through dental procedures.Materials and methodsNeural crest stem cells were obtained from human excised third molars and differentiated in culture using a protocol for directed differentiation into cardiomyocytes. Differentiation of cells was assessed through gene expression and immunostaining studies. Optical stimulation using pulsed infrared radiation (IR) (λ = 1863 nm) was delivered to cell aggregates to study their contractile ability.ResultsWe show that neural crest stem cells can be differentiated to a cardiomyogenic lineage, which was verified through immunostaining and gene expression. We observed a significant increase in cardiomyocyte-specific markers, NK2 homeobox 5 (NKX2.5) and troponin T type 2 (TNNT2), with positive changes in tropomyosin I (TPM1), gap junction protein alpha 1/Cx43 (GJA1/Cx43), and myocyte enhancement factor 2C (MEF2C). Furthermore, we were able to elicit and maintain pulse-by-pulse contractile responses in the derived cells, including in cardiospheres, with pulsed IR delivered at various radiant energies. The contractility in responses to IR could be maintained at different frequencies (0.25-2 Hz) and up to 10-min durations. While these cells did not maintain their contractility following cessation of IR, these cells demonstrated responses to the optical stimuli that are consistent with previous reports. We also found no evidence for irreversible mitochondrial depolarization in these cells following the long duration of infrared stimulation, suggesting the robustness of these cells.ConclusionsOverall, these results suggest the merit of neural crest-derived stem cells for cardiomyogenic applications and a potential cell source for repair that should contribute to efforts to translate cell-based strategies to the clinic.

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

Publications

A novel cardiomyogenic role for Isl1<sup>+</sup> neural crest cells in the inflow tract.

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Dataset Information

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

Publications

A novel cardiomyogenic role for Isl1<sup>+</sup> neural crest cells in the inflow tract.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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