Embryonic heart progenitors and cardiogenesis (original) (raw)
Related papers
Developmental Dynamics, 2009
There is scant information on the fate of cardiac progenitor cells (CPC) in the embryonic heart after chamber specification. Here we simultaneously tracked three lineage-specific markers (Nkx2.5, MLC2v, and ANF) and confirmed that CPCs with an Nkx2.5 1 MLC2v 2 ANF 2 phenotype are present in the embryonic (E) day 11.5 mouse ventricular myocardium. We demonstrated that these CPCs could give rise to working cardiomyocytes and conduction system cells. Using a two-photon imaging analysis, we found that the majority of CPCs are not capable of developing Ca 21 transients in response to b-adrenergic receptor stimulation. In contrast, Nkx2.5 1 cells expressing MLC2v but not ANF are capable of developing functional Ca 21 transients. We showed that Ca 21 transients could be invoked in Nkx2.5 1 MLC2v 1 ANF 1 cells only upon inhibition of Gi, muscarinic receptors, or nitric oxide synthase (NOS) signaling pathways. Our data suggest that these inhibitory pathways may delay functional specification in a subset of developing ventricular cells.
Early cardiac development: a view from stem cells to embryos
Cardiovascular Research
From the 1920s, early cardiac development has been studied in chick and, later, in mouse embryos in order to understand the first cell fate decisions that drive specification and determination of the endocardium, myocardium, and epicardium. More recently, mouse and human embryonic stem cells (ESCs) have demonstrated faithful recapitulation of early cardiogenesis and have contributed significantly to this research over the past few decades. Derived almost 15 years ago, human ESCs have provided a unique developmental model for understanding the genetic and epigenetic regulation of early human cardiogenesis. Here, we review the biological concepts underlying cell fate decisions during early cardiogenesis in model organisms and ESCs. We draw upon both pioneering and recent studies and highlight the continued role for in vitro stem cells in cardiac developmental biology.
Role of Stem Cells in Cardiac Diseases
International Journal of Stem Cell Research and Transplantation, 2016
The heart is the first organ to become fully functional during development in all organisms. Despite numerous studies in model organisms in the last two decades, the identity of the cardiac progenitor cell (CPC) remains unclear. However, studies have confirmed that most cardiac cells originate from the mesoderm. Work in recent years has shed light on a few genetic markers that are believed to be candidates for expression on the illusive cardiac progenitor cell, such as NKX 2.5, ISL-1, FLK-1, MESP1 and others [1-4]. In mouse embryonic development, cardiac progenitor cells (CPC) are believed to make their debut in a 24-hour window between days E6.5 and E7.5. Reports have indicated that the precursors for the heart forming cells must express MESP1. MESP1 expressing cells exist at day 6.5 in the primitive streak [5]. These cells, however, can give rise to non-cardiac lineages and thus MESP1 could be a marker of a progenitor cell that is upstream of the CPC [6]. As cells migrate away from the primitive streak and into the Anterior Lateral Plate Mesoderm, MESP1 expression drops and cardi
Building and Repairing the Heart: What Can We Learn from Embryonic Development
Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs) in vitro model system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed. BioMed Research International, Volume 2014, http://dx.doi.org/10.1155/2014/679168
PloS one, 2011
Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in ...
Cardiovascular Research, 2003
Despite the advances in cardiovascular treatment, cardiac disease remains a major cause of morbidity in all industrialized countries. The extraordinary potential of (embryonic) stem cells for therapeutic purposes has revolutionized ideas about cardiac repair of diseased cardiac muscle to exciting stages. This, in turn, has challenged research on cardiac differentiation of stem cells. For instance, cultures of mouse embryonic stem cells quite easily differentiate into the cardiogenic lineage, as assessed by their potential to beat spontaneously. However, repair of impaired cardiac muscle by spontaneously beating cardiac muscle cells might impose severe risks upon a human patient. Therefore, it is of crucial importance to understand the mechanisms that underlie the development of the distinct cardiac muscle cell types of the adult mammalian heart. In this review we tried to relate cardiac morphogenesis to the development of unique molecular phenotypes of cardiomyocytes. This relationship will provide a framework to assess the significance of the molecular phenotypes that are observed in embryonic stem cell-derived cardiomyocytes (ESDCs). Although for the phenotyping of ESDCs a comparison should be made with the phenotypes of the developing heart, so far none of the currently available markers allow unequivocal assignment of subtypes.
Foetal and adult cardiomyocyte progenitor cells have different developmental potential
Journal of Cellular and Molecular Medicine, 2010
In the past years, cardiovascular progenitor cells have been isolated from the human heart and characterized. Up to date, no studies have been reported in which the developmental potential of foetal and adult cardiovascular progenitors was tested simultaneously. However, intrinsic differences will likely affect interpretations regarding progenitor cell potential and application for regenerative medicine. Here we report a direct comparison between human foetal and adult heart-derived cardiomyocyte progenitor cells (CMPCs). We show that foetal and adult CMPCs have distinct preferences to differentiate into mesodermal lineages. Under pro-angiogenic conditions, foetal CMPCs form more endothelial but less smooth muscle cells than adult CMPCs. Foetal CMPCs can also develop towards adipocytes, whereas neither foetal nor adult CMPCs show significant osteogenic differentiation. Interestingly, although both cell types differentiate into heart muscle cells, adult CMPCs give rise to electrophysiologically more mature cardiomyocytes than foetal CMPCs. Taken together, foetal CMPCs are suitable for molecular cell biology and developmental studies. The potential of adult CMPCs to form mature cardiomyocytes and smooth muscle cells may be essential for cardiac repair after transplantation into the injured heart.