Properties of Cardiac Progenitor Cells in the Second Heart Field

Francou, Alexandre; Kelly, Robert G.

doi:10.1007/978-4-431-54628-3_23

Cited by 5 publications

(2 citation statements)

References 20 publications

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“…Downstream, SHF addition to both poles of the heart is dependent on the transcription factor Isl1 in mice [19], whilst isl1a is required only for venous pole addition in zebrafish with isl2b driving arterial SHF addition [13,20]. SHF addition and cardiac morphogenesis are tightly linked, with defects in SHF addition leading to heart malformations and congenital heart disease [21].…”

Section: Introductionmentioning

confidence: 99%

Lamb1a regulates atrial growth by limiting excessive, contractility-dependent second heart field addition during zebrafish heart development

Derrick

Ejg

Ass

et al. 2021

Preprint

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During early vertebrate heart development, the heart transitions from a linear tube to a complex asymmetric structure. This process includes looping of the tube and ballooning of the emerging cardiac chambers, which occur simultaneously with growth of the heart. A key driver of cardiac growth is deployment of cells from the Second Heart Field (SHF) into both poles of the heart, with cardiac morphogenesis and growth intimately linked in heart development. Laminin is a core component of extracellular matrix (ECM) basement membranes, and although mutations in specific laminin subunits are linked with a variety of cardiac abnormalities, including congenital heart disease and dilated cardiomyopathy, no role for laminin has been identified in early vertebrate heart morphogenesis. We identified dynamic, tissue-specific expression of laminin subunit genes in the developing zebrafish heart, supporting a role for laminins in heart morphogenesis. lamb1a mutants exhibit cardiomegaly from 2dpf onwards, with subsequent progressive defects in cardiac morphogenesis characterised by a failure of the chambers to compact around the developing atrioventricular canal. We show that loss of lamb1a results in excess addition of SHF cells to the atrium, revealing that Lamb1a functions to limit heart size during cardiac development by restricting SHF addition to the venous pole. lamb1a mutants exhibit hallmarks of altered haemodynamics, and specifically blocking cardiac contractility in lamb1a mutants rescues heart size and atrial SHF addition. Furthermore, we identify that FGF and RA signalling, two conserved pathways promoting SHF addition, are regulated by heart contractility and are dysregulated in lamb1a mutants, suggesting that laminin mediates interactions between SHF deployment, heart biomechanics, and biochemical signalling during heart development. Together, this describes the first requirement for laminins in early vertebrate heart morphogenesis, reinforcing the importance of specialised ECM composition in cardiac development.

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Section: Introductionmentioning

confidence: 99%

Lamb1a regulates atrial growth by limiting excessive, contractility-dependent second heart field addition during zebrafish heart development

Derrick

Ejg

Ass

et al. 2021

Preprint

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“…To be able to derive the different cardiac subpopulations from hiPSCs, it is necessary to understand how they develop in the early embryo. Cell fate mapping and gene targeting studies in rodents and avian models have provided important insights into the origin of different regions of the heart and showed that many cardiac cells originate from distinct progenitor populations (first and second heart field, FHF and SHF, respectively) that are specified early in development (Francou & Kelly, 2016; Kelly, Buckingham, & Moorman, 2014; Meilhac & Buckingham, 2018; Waardenberg, Ramialison, Bouveret, & Harvey, 2014). Protocols for different cell lineages from hiPSCs have been described, with variable success.…”

Section: Lessons Learned From Hipsc Differentiation To Multiple Cardi...mentioning

confidence: 99%

Translational potential of hiPSCs in predictive modeling of heart development and disease

Mansfield

Zhao

Basu

2022

Birth Defects Research

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Congenital heart disease (CHD) represents a major class of birth defects worldwide and is associated with cardiac malformations that often require surgical intervention immediately after birth. Despite the intense efforts from multicentric genome/exome sequencing studies that have identified several genetic variants, the etiology of CHD remains diverse and often unknown. Genetically modified animal models with candidate gene deficiencies continue to provide novel molecular insights that are responsible for fetal cardiac development. However, the past decade has seen remarkable advances in the field of human induced pluripotent stem cell (hiPSC)‐based disease modeling approaches to better understand the development of CHD and discover novel preventative therapies. The iPSCs are derived from reprogramming of differentiated somatic cells to an embryonic‐like pluripotent state via overexpression of key transcription factors. In this review, we describe how differentiation of hiPSCs to specialized cardiac cellular identities facilitates our understanding of the development and pathogenesis of CHD subtypes. We summarize the molecular and functional characterization of hiPSC‐derived differentiated cells in support of normal cardiogenesis, those that go awry in CHD and other heart diseases. We illustrate how stem cell‐based disease modeling enables scientists to dissect the molecular mechanisms of cell–cell interactions underlying CHD. We highlight the current state of hiPSC‐based studies that are in the verge of translating into clinical trials. We also address limitations including hiPSC‐model reproducibility and scalability and differentiation methods leading to cellular heterogeneity. Last, we provide future perspective on exploiting the potential of hiPSC technology as a predictive model for patient‐specific CHD, screening pharmaceuticals, and provide a source for cell‐based personalized medicine. In combination with existing clinical and animal model studies, data obtained from hiPSCs will yield further understanding of oligogenic, gene–environment interaction, pathophysiology, and management for CHD and other genetic cardiac disorders.

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Genetics of Transposition of Great Arteries: Between Laterality Abnormality and Outflow Tract Defect

Ita

Cisneros

Rosas-Vargas

2020

J. of Cardiovasc. Trans. Res.

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Properties of Cardiac Progenitor Cells in the Second Heart Field

Cited by 5 publications

References 20 publications

Lamb1a regulates atrial growth by limiting excessive, contractility-dependent second heart field addition during zebrafish heart development

Lamb1a regulates atrial growth by limiting excessive, contractility-dependent second heart field addition during zebrafish heart development

Translational potential of hiPSCs in predictive modeling of heart development and disease

Genetics of Transposition of Great Arteries: Between Laterality Abnormality and Outflow Tract Defect

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