Cardiac Cell Lineages that Form the Heart

Meilhac, Sigolène M.; Lescroart, Fabienne; Blanpain, Cédric; Buckingham, Margaret

doi:10.1101/cshperspect.a013888

Cited by 73 publications

(65 citation statements)

References 101 publications

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“…An anatomically and functionally normal heart is the result of a coordinated series of specification events and cell movements that begin as early as gastrulation (Meilhac et al, 2014;Vincent and Buckingham, 2010). Fate mapping of the early mouse embryo revealed the organized manner in which cells of the epiblast migrate through the primitive streak (PS) to become members of the separate germ layers (Lawson et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Notch Signaling Commits Mesoderm to the Cardiac Lineage

Bardot

Jadhav

Wickramasinghe

et al. 2020

Preprint

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statementEarly fate decisions are dictated by the embryonic signaling environment. We show that Notch signaling is active during early mouse development and that activating Notch in human cardiac mesoderm enhances cardiomyocyte differentiation efficiency. AbstractDuring development multiple progenitor populations contribute to the formation of the four-chambered heart and its diverse lineages. However, the underlying mechanisms that result in the specification of these progenitor populations are not yet fully understood. We have previously identified a population of cells that gives rise selectively to the heart ventricles but not the atria. Here, we have used this knowledge to transcriptionally profile subsets of cardiac mesoderm from the mouse embryo and have identified an enrichment for Notch signaling components in ventricular progenitors. Using directed differentiation of human pluripotent stem cells, we next investigated the role of Notch in cardiac mesoderm specification in a temporally controlled manner. We show that transient Notch induction in mesoderm increases cardiomyocyte differentiation efficiency, while maintaining cardiomyocytes in an immature state. Finally, our data suggest that Notch interacts with WNT to enhance commitment to the cardiac lineage. Overall, our findings support the notion that key signaling events during early heart development are critical for proper lineage specification and provide evidence for early roles of Notch and WNT during mouse and human heart development.

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Section: Introductionmentioning

confidence: 99%

Notch Signaling Commits Mesoderm to the Cardiac Lineage

Bardot

Jadhav

Wickramasinghe

et al. 2020

Preprint

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“…CHDs are formed when complex cellular and molecular processes underlying embryonic heart development are disturbed. The heart is developed from three pools of progenitor cells: the first heart field (FHF), the second heart field (SHF) and cardiac neural crest (CNC) [4]. The FHF progenitors initially form the primary heart tube.…”

Section: Introductionmentioning

confidence: 99%

Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes in Mice

Engineer¹,

Saiyin²,

Lu³

et al. 2018

Preprint

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word count: 248Main text word count: 4,612Figures: 9; Tables: 1 Supplementary Table: 1; Supplementary Figure: 1References: 50All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/304006 doi: bioRxiv preprint first posted online Apr. 18, 2018; 2 ABSTRACT Aims: Tetrahydrobiopterin (BH4) is a co-factor of endothelial nitric oxide synthase (eNOS), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan®), an orally active synthetic form of BH4 on eNOS uncoupling and congenital heart defects (CHDs) induced by pregestational diabetes in mice.Methods: Adult female mice were induced to pregestational diabetes by streptozotocin and bred with normal males to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHDs were identified by histological analysis. Cell proliferation, eNOS dimerization and reactive oxygen species (ROS) production were assessed in the fetal heart. Results:Pregestational diabetes results in a spectrum of CHDs in their offspring. Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHDs from 59% to 27% and major abnormalities, such as atrioventricular septal defect and double outlet right ventricle were absent in the sapropterin treated group. Lineage tracing reveals that pregestational diabetes results in decreased commitment of second heart field progenitors to the outflow tract, endocardial cushions, and ventricular myocardium of the fetal heart. Notably, decreased cell proliferation and cardiac transcription factor expression induced by maternal diabetes were normalized with sapropterin treatment. Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered ROS levels in the fetal heart.Conclusions: Sapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation and prevents the development of CHDs in the offspring. Thus, sapropterin may have therapeutic potential in preventing CHDs in pregestational diabetes.

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“…[17] Further, mouse embryos can also be employed in lineage tracing studies, from which it is possible to determine the origin of cells that form the heart and the valves. [18] However, mouse embryos are difficult to access inside the uterus , precluding non-invasive in vivo imaging of cardiac function and blood flow conditions during early embryonic stages. Zebra fish and chicken embryos, on the other hand, are easy to access for in vivo imaging that minimally disturbs their environment during early stages of development,[19–27] making them ideal models to study embryonic changes that lead to cardiac defects.…”

Section: Small Animal Models For Studying Cardiac Valve Developmentmentioning

confidence: 99%

Animal models for heart valve research and development

Kheradvar

Zareian

Kawauchi

et al. 2017

Drug Discovery Today: Disease Models

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Valvular heart disease is the third-most common cause of heart problems in the United States. Malfunction of the valves can be acquired or congenital and each may lead either to stenosis or regurgitation, or even both in some cases. Heart valve disease is a progressive disease, which is irreversible and may be fatal if left untreated. Pharmacological agents cannot currently prevent valvular calcification or help repair damaged valves, as valve tissue is unable to regenerate spontaneously. Thus, heart valve replacement/repair is the only current available treatment. Heart valve research and development is currently focused on two parallel paths; first, research that aims to understand the underlying mechanisms for heart valve disease to emerge with an ultimate goal to devise medical treatment; and second, efforts to develop repair and replacement options for a diseased valve. Studies that focus on developmental malformation, genetic and disease epigenetics usually employ small animal models that are easy to access for in vivo imaging that minimally disturbs their environment during early stages of development. Alternatively, studies that aim to develop novel device for replacement and repair of diseased valves often employ large animals whose heart size and anatomy closely replicate human’s. This paper aims to briefly review the current state-of-the-art animal models, and justification to use an animal model for a particular heart valve related project.

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Cardiac Cell Lineages that Form the Heart

Cited by 73 publications

References 101 publications

Notch Signaling Commits Mesoderm to the Cardiac Lineage

Notch Signaling Commits Mesoderm to the Cardiac Lineage

Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes in Mice

Animal models for heart valve research and development

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