Dissecting the Complexity of Early Heart Progenitor Cells

Abstract

Early heart development depends on the coordinated participation of heterogeneous cellsources. As pioneer work from Adriana C. Gittenberger-de Groot demonstrated, characterizing thesedistinct cell sources helps us to understand congenital heart defects. Despite decades of researchon the segregation of lineages that form the primitive heart tube, we are far from understanding itsfull complexity. Currently, single-cell approaches are providing an unprecedented level of detail oncellular heterogeneity, offering new opportunities to decipher its functional role. In this review, wewill focus on three key aspects of early heart morphogenesis: First, the segregation of myocardial andendocardial lineages, which yields an early lineage diversification in cardiac development; second,the signaling cues driving differentiation in these progenitor cells; and third, the transcriptionalheterogeneity of cardiomyocyte progenitors of the primitive heart tube. Finally, we discuss howsingle-cell transcriptomics and epigenomics, together with live imaging and functional analyses, willlikely transform the way we delve into the complexity of cardiac development and its links withcongenital defects.

Cardiac competence of the paraxial head mesoderm fades concomitant with a shift towards the head skeletal muscle programme

“…established the normal developmental programmes or trajectories of cells left undisturbed. These studies showed that cells gastrulating from the HH3 chicken primitive streak and settling in a position lateral to the boundary of the overlying neural plate will deliver the primitive heart that starts beating at HH10 ((Camp et al, 2012; Garcia-Martinez and Schoenwolf, 1993); reviewed in (Sendra et al, 2021; Wittig and Münsterberg, 2020)). In contrast, cells that settle in a paraxial position contribute to the skull and to craniofacial skeletal muscles (reviewed in (Schubert et al, 2018).…”

“…The vertebrate head mesoderm is the first embryonic mesoderm type to emerge during gastrulation (Camp et al, 2012; Garcia-Martinez and Schoenwolf, 1993). It delivers the heart (reviewed in (Meilhac and Buckingham, 2018; Sendra et al, 2021; Spater et al, 2014)), the great vessels (Paffett-Lugassy et al, 2013; Wang et al, 2017), the smooth muscle collar of the cardiac outflow (Wang et al, 2017), genuine craniofacial and oesophageal skeletal muscles (reviewed in (Schubert et al, 2018)) and parts of the skull ((Jandzik et al, 2015); reviewed in (Kuratani, 2005)), with cardiac cells originating from the lateral, and skeletal muscle and also bone/cartilage mainly from the paraxial region of the tissue (reviewed in (Evans and Noden, 2006)). The primitive heart, blood and vascular system are the first fully functional organs in the embryo, and defects in their development are incompatible with life.…”

“…The primitive heart, blood and vascular system are the first fully functional organs in the embryo, and defects in their development are incompatible with life. In recent years, the head mesoderm has received quite some attention since a subpopulation of cardiogenic cells, often referred to as secondary heart field (SHF) cells and located in the pharyngeal arches at the junction to the primitive heart, seem to be multipotent cardiac-skeletal muscle-vascular endothelial precursor or stem cells (reviewed in (Sendra et al, 2021)). When these cells are recruited into the primitive heart, they deliver the mature in- and outflow tract, in mammals and birds also encompassing the right ventricle.…”

“…Cells fated to contribute to the heart are specified, but not yet determined, as cardiogenic cells when they leave the primitive streak ((Lopez-Sanchez et al, 2009; Wang et al, 2013); reviewed in (Sendra et al, 2021)). Migration to their target area lateral to the developing neural plate is controlled by bone morphogenetic proteins (Bmp; ((Song et al, 2014)).…”

Cardiac differentiation roadmap for analysis of plasticity and balanced lineage commitment

“…These progenitor states and their lineage contributions have been studied using single-cell omics approaches in mouse embryonic tissues, as reviewed recently (Lescroart & Zaffran, 2022;Sendra et al, 2021;Tyser, 2023). The lineages of the FHF primarily populate the left ventricle and part of the atria.…”