Cardiac embryogenesis

ESC CardioMed ◽  
2018 ◽  
pp. 33-36
Author(s):  
Robert G. Kelly
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Congenital Heart ◽  
Heart Defects ◽  
Embryonic Heart ◽  
Heart Tube ◽  
Second Heart Field ◽  
Heart Field ◽  
Cell Niche ◽  
The Right

The embryonic heart forms in anterior lateral splanchnic mesoderm and is derived from Mesp1-expressing progenitor cells. During embryonic folding, the earliest differentiating progenitor cells form the linear heart tube in the ventral midline. The heart tube extends in length and loops to the right as new myocardium is progressively added at the venous and arterial poles from multipotent second heart field cardiovascular progenitor cells in contiguous pharyngeal mesoderm. While the linear heart tube gives rise to the left ventricle, the right ventricle, outflow tract, and a large part of atrial myocardium are derived from the second heart field. Progressive myocardial differentiation is controlled by intercellular signals within the progenitor cell niche. The embryonic heart is the template for septation and growth of the four-chambered definitive heart and defects in progenitor cell deployment result in a spectrum of common forms of congenital heart defects.

Cardiac embryogenesis

ESC CardioMed ◽  
2018 ◽  
pp. 33-36
Author(s):  
Robert G. Kelly
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Congenital Heart ◽  
Heart Defects ◽  
Embryonic Heart ◽  
Heart Tube ◽  
Second Heart Field ◽  
Heart Field ◽  
Cell Niche ◽  
The Right

The embryonic heart forms in anterior lateral splanchnic mesoderm and is derived from Mesp1-expressing progenitor cells. During embryonic folding, the earliest differentiating progenitor cells form the linear heart tube in the ventral midline. The heart tube extends in length and loops to the right as new myocardium is progressively added at the venous and arterial poles from multipotent second heart field cardiovascular progenitor cells in contiguous pharyngeal mesoderm. While the linear heart tube gives rise to the left ventricle, the right ventricle, outflow tract, and a large part of atrial myocardium are derived from the second heart field. Progressive myocardial differentiation is controlled by intercellular signals within the progenitor cell niche. The embryonic heart is the template for septation and growth of the four-chambered definitive heart and defects in progenitor cell deployment result in a spectrum of common forms of congenital heart defects.

Incorporation of myocardial progenitors at the arterial pole of the heart

2018 ◽  
Author(s):  
Mayyasa Rammah ◽  
Francesca Rochais ◽  
Robert G. Kelly
Keyword(s):  
Heart Defects ◽  
Outflow Tract ◽  
Signalling Pathways ◽  
Second Heart Field ◽  
Proliferation And Differentiation ◽  
Life Threatening ◽  
Heart Field ◽  
Cell Niche ◽  
The Right ◽  
Epithelial Progenitor Cells

The arterial pole of the heart is a hotspot for life-threatening forms of congenital heart defects (CHDs). It is formed by progressive addition of myocardium from epithelial progenitor cells in the second heart field (SHF). SHF cells contribute successively to the right ventricle and proximal and distal outflow tract myocardial walls which, after neural crest influx and cardiac septation, give rise to myocardium at the base of the aorta and pulmonary trunk. SHF cells are characterized by continued proliferation and differentiation delay controlled by an array of transcriptional regulators and signalling pathways which define the SHF progenitor cell niche in pharyngeal mesoderm. Failure of normal SHF deployment leads to a shortened outflow tract and failure of ventriculo-arterial alignment, resulting in a spectrum of conotruncal CHD. We discuss the origins of the SHF in cardiopharyngeal mesoderm and focus on the mechanisms driving SHF deployment, summarizing current understanding of critical signalling pathways and transcription factors.

scholarly journals Outflow Tract Formation—Embryonic Origins of Conotruncal Congenital Heart Disease

2021 ◽  
Vol 8 (4) ◽  
pp. 42
Author(s):  
Sonia Stefanovic ◽  
Heather C. Etchevers ◽  
Stéphane Zaffran
Keyword(s):  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Dynamic Structure ◽  
Cell Types ◽  
Outflow Tract ◽  
Heart Tube ◽  
Heart Field ◽  
Multiple Cell ◽  
The Many

Anomalies in the cardiac outflow tract (OFT) are among the most frequent congenital heart defects (CHDs). During embryogenesis, the cardiac OFT is a dynamic structure at the arterial pole of the heart. Heart tube elongation occurs by addition of cells from pharyngeal, splanchnic mesoderm to both ends. These progenitor cells, termed the second heart field (SHF), were first identified twenty years ago as essential to the growth of the forming heart tube and major contributors to the OFT. Perturbation of SHF development results in common forms of CHDs, including anomalies of the great arteries. OFT development also depends on paracrine interactions between multiple cell types, including myocardial, endocardial and neural crest lineages. In this publication, dedicated to Professor Andriana Gittenberger-De Groot and her contributions to the field of cardiac development and CHDs, we review some of her pioneering studies of OFT development with particular interest in the diverse origins of the many cell types that contribute to the OFT. We also discuss the clinical implications of selected key findings for our understanding of the etiology of CHDs and particularly OFT malformations.

scholarly journals Tbx2 misexpression impairs deployment of second heart field derived progenitor cells to the arterial pole of the embryonic heart

2009 ◽  
Vol 333 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Laurent Dupays ◽  
Surendra Kotecha ◽  
Brigitt Angst ◽  
Timothy J. Mohun
Keyword(s):  
Progenitor Cells ◽  
Embryonic Heart ◽  
Second Heart Field ◽  
Heart Field

scholarly journals Maternal hyperglycemia impedes second heart field-derived cardiomyocyte differentiation to elevate the risk of congenital heart defects

2021 ◽  
Author(s):  
Sathiyanarayanan Manivannan ◽  
Corrin Mansfield ◽  
Xinmin Zhang ◽  
Karthik M. Kodigepalli ◽  
Uddalak Majumdar ◽  
...  
Keyword(s):  
Congenital Heart ◽  
Heart Defects ◽  
Lineage Tracing ◽  
Ventricular Wall ◽  
Cardiomyocyte Differentiation ◽  
Glucose Levels ◽  
Second Heart Field ◽  
Maternal Hyperglycemia ◽  
Wall Thinning ◽  
Heart Field

Congenital heart disease (CHD) is the most frequently occurring structural malformations of the heart affecting ~1% of live births. Besides genetic predisposition, embryonic exposure to teratogens during pregnancy increases the risk of CHD. However, the dose and cell-type-specific responses to an adverse maternal environment remain poorly defined. Here, we report a dose-response relationship between maternal glucose levels and phenotypic severity of CHD in offspring, using a chemically-induced pregestational diabetes mellitus (PGDM) mouse model. Embryos from dams with low-level maternal hyperglycemia (matHG) displayed trabeculation defects, ventricular wall thinning, and ventricular septal defects (VSD). On the other hand, embryos from dams with high-level matHG display outflow tract malformations, ventricular wall thinning and an increased rate of VSD. Our findings show that increasing levels of matHG exacerbates CHD occurrence and severity in offspring compared to control embryos. We applied single-cell RNA- sequencing to define matHG-related transcriptional differences in E9.5 and E11.5 hearts as comparing to controls. Disease-dependent gene-expression changes were observed in Isl1+ second heart field (SHF) and Tnnt2+ cardiomyocyte subpopulations. Lineage tracing studies in Isl1-Cre; RosamTmG embryonic hearts showed Isl1+-SHF-derived cardiomyocyte differentiation was impaired with matHG. This study highlights the influence of matHG-dosage on cardiac morphogenesis and identifies perturbations in the Isl1-dependent gene-regulatory network that affect SHF-derived cardiomyocyte differentiation contributing to matPGDM-induced CHD.

scholarly journals Hox-dependent coordination of cardiac progenitor cell patterning and differentiation

2020 ◽  
Author(s):  
Sonia Stefanovic ◽  
Brigitte Laforest ◽  
Jean-Pierre Desvignes ◽  
Fabienne Lescroart ◽  
Laurent Argiro ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Heart Defects ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Cardiac Differentiation ◽  
Cardiac Progenitor Cells ◽  
Heart Tube ◽  
Atrioventricular Septal Defects ◽  
Genome Wide ◽  
Heart Field

SUMMARYPerturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.

scholarly journals Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sonia Stefanovic ◽  
Brigitte Laforest ◽  
Jean-Pierre Desvignes ◽  
Fabienne Lescroart ◽  
Laurent Argiro ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Heart Defects ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Cardiac Differentiation ◽  
Cardiac Progenitor Cells ◽  
Heart Tube ◽  
Atrioventricular Septal Defects ◽  
Genome Wide ◽  
Heart Field

Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.

scholarly journals A Role for the Cytoskeleton in Heart Looping

2007 ◽  
Vol 7 ◽  
pp. 280-298 ◽  
Author(s):  
Kersti K. Linask ◽  
Michael VanAuker
Keyword(s):  
Heart Development ◽  
Cell Biology ◽  
Heart Defects ◽  
Heart Tube ◽  
Second Heart Field ◽  
The Past ◽  
Complex Process ◽  
Nonmuscle Myosin Ii ◽  
Heart Looping ◽  
Heart Field

Over the past 10 years, key genes involved in specification of left-right laterality pathways in the embryo have been defined. The read-out for misexpression of laterality genes is usually the direction of heart looping. The question of how dextral looping direction occurred mechanistically and how the heart tube bends remains unknown. It is becoming clear from our experiments and those of others that left-right differences in cell proliferation in the second heart field (anterior heart field) drives the dextral direction. Evidence is accumulating that the cytoskeleton is at the center of laterality, and the bending and rotational forces associated with heart looping. If laterality pathways are modulated upstream, the cytoskeleton, including nonmuscle myosin II (NMHC-II), is altered downstream within the cardiomyocytes, leading to looping abnormalities. The cytoskeleton is associated with important mechanosensing and signaling pathways in cell biology and development. The initiation of blood flow during the looping period and the inherent stresses associated with increasing volumes of blood flowing into the heart may help to potentiate the process. In recent years, the steps involved in this central and complex process of heart development that is the basis of numerous congenital heart defects are being unraveled.

scholarly journals Cardiac progenitors auto-regulate second heart field cell fate via Wnt secretion

2021 ◽  
Author(s):  
Matthew Miyamoto ◽  
Suraj Kannan ◽  
Hideki Uosaki ◽  
Tejasvi Kakani ◽  
Sean Murphy ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Congenital Heart ◽  
Heart Defects ◽  
Cardiac Marker ◽  
Cardiac Progenitors ◽  
Second Heart Field ◽  
Heart Field ◽  
Heart Formation

Proper heart formation requires coordinated development of two anatomically distinct groups of cells - the first and second heart fields (FHF and SHF). Given that congenital heart defects are often restricted to derivatives of the FHF or SHF, it is crucial to understand the mechanisms controlling their development. Wnt signaling has previously been implicated in SHF proliferation; however, the source of Wnts remains unknown. Through comparative gene analysis, we found upregulation of Wnts and Wnt receptor/target genes in the FHF and SHF, respectively, raising the possibility that early cardiac progenitors may secrete Wnts to influence SHF cell fate. To probe this further, we deleted Wntless (Wls), a gene required for Wnt ligand secretion, in various populations of precardiac cells. Deletion of Wls in Mesp1+ cells resulted in formation of a single chamber heart with left ventricle identity, implying compromised SHF development. This phenotype was recapitulated by deleting Wls in cells expressing Islet1, a pan-cardiac marker. Similarly, Wls deletion in cells expressing Nkx2.5, a later-expressed pan-cardiac marker, resulted in hypoplastic right ventricle, a structure derived from the SHF. However, no developmental defects were observed when deleting Wls in SHF progenitors. To gain mechanistic insights, we isolated Mesp1-lineage cells from developing embryos and performed single-cell RNA-sequencing. Our comprehensive single cell transcriptome analysis revealed that Wls deletion dysregulates developmental trajectories of both anterior and posterior SHF cells, marked by impaired proliferation and premature differentiation. Together, these results demonstrate a critical role of local precardiac mesodermal Wnts in SHF fate decision, providing fundamental insights into understanding heart field development and chamber formation.Significance StatementThere is significant interest in understanding the mechanisms underlying heart formation to develop treatments and cures for patients suffering from congenital heart disease. In particular, we were interested in the intricacies of first (FHF) and second heart field (SHF) development, as many congenital heart defects present with heart field-specific etiologies. Here, we uncovered a novel relationship between specified cardiac progenitor cells and second heart field progenitors. Through genetic manipulation of Wnt secretion in developing mouse embryos, we identified a population of cardiac progenitor cells that acts as a local source of Wnts which are necessary for proper SHF development. Our single cell transcriptomic analysis of developing anterior mesoderm showed cardiac progenitor-secreted Wnts function through regulation of differentiation and proliferation among SHF progenitors. Thus, this study provides insight into the source and timing of Wnts required for SHF development, and points to the crucial role of co-developing cell populations in heart development.

In Vivo Evaluation of Bioprinted Cardiac Patches Composed of Cardiac-Specific Extracellular Matrix and Progenitor Cells in a Model of Pediatric Heart Failure

2021 ◽  
Author(s):  
Donald Bejleri ◽  
Matthew Robeson ◽  
Milton Brown ◽  
Jervaughn Hunter ◽  
Joshua Maxwell ◽  
...  
Keyword(s):  
Heart Failure ◽  
Extracellular Matrix ◽  
Congenital Heart ◽  
Pediatric Patients ◽  
Heart Defects ◽  
In Vivo Evaluation ◽  
Surgical Methods ◽  
Pediatric Heart Failure ◽  
The Right

Pediatric patients with congenital heart defects (CHD) often present with heart failure from increased load on the right ventricle (RV) due to both surgical methods to treat CHD and the...

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