When Does the Human Embryonic Heart Start Beating? A Review of Contemporary and Historical Sources of Knowledge About the Onset of Blood Circulation in Man

Männer, Jörg

doi:10.20944/preprints202205.0031.v1

Cited by 5 publications

(1 citation statement)

References 73 publications

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“…5c) . In general, and except for EMM1 organoids, developmentally induced organoids presented beating rates compatible with what has been described for early human embryos at GD45 90, 91 (60-80 beats per minute). In addition to calcium, the total electrophysiological response of the cardiomyocyte action potential incorporates additional ion currents such as potassium and sodium.…”

Section: Resultssupporting

confidence: 83%

A patterned human heart tube organoid model generated by pluripotent stem cell self-assembly

Volmert

Aguirre

Riggs

et al. 2022

Preprint

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Human pluripotent stem cells can recapitulate significant features of mammalian organ development in vitro, including key aspects of heart development. We hypothesized that the organoids thus created can be made substantially more relevant by mimicking aspects of in utero gestation, leading to higher physiological and anatomical resemblance to their in vivo counterparts. Here, we report steps towards generating developmentally inspired maturation methodologies to differentiate early human heart organoids into patterned heart-tube-like structures in a reproducible and high-throughput fashion by complete self-organization. The maturation strategy consists of the controlled and stepwise exposure to metabolic (glucose, fatty acids) and hormonal signals (T3, IGF-1) as present during early heart development. These conditions elicit important transcriptomic, cellular, morphological, metabolomic, and functional changes over a 10-day period consistent with continuously increasing heart complexity, maturation, and patterning. Our data reveals the emergence of atrial and ventricular cardiomyocyte populations, valvular cells, epicardial cells, proepicardial-derived cells, endothelial cells, stromal cells, conductance cells, and cardiac progenitors, all of them cell types present in the primitive heart tube. Anatomically, the organoids elongate and develop well-differentiated atrial and ventricular chambers with compacted myocardial muscle walls and a proepicardial organ. For the first time in a completely self-organizing heart organoid, we show anterior-posterior patterning due to an endogenous retinoic acid gradient originating at the atrial pole, where proepicardial and atrial populations reside, mimicking the developmental process present within the primitive heart tube. Collectively, these findings highlight the ability of self-organization and developmental maturation strategies to recapitulate human heart development. Our patterned human heart tube model constitutes a powerful in vitro tool for dissecting the role of different cell types and genes in human heart development, as well as disease modeling congenital heart defects, and represents a step forward in creating fully synthetic human hearts.

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Section: Resultssupporting

confidence: 83%

A patterned human heart tube organoid model generated by pluripotent stem cell self-assembly

Volmert

Aguirre

Riggs

et al. 2022

Preprint

View full text Add to dashboard Cite

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Formation of the Heart: Defining Cardiomyocyte Progenitors at Single-Cell Resolution

Tyser

2023

Curr Cardiol Rep

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Purpose of Review Formation of the heart requires the coordinated addition of multiple progenitor sources which have undergone different pathways of specification and differentiation. In this review, I aim to put into context how recent studies defining cardiac progenitor heterogeneity build on our understanding of early heart development and also discuss the questions raised by this new insight. Recent Findings With the development of sequencing technologies and imaging approaches, it has been possible to define, at high temporal resolution, the molecular profile and anatomical location of cardiac progenitors at the single-cell level, during the formation of the mammalian heart. Summary Given the recent progress in our understanding of early heart development and technical advances in high-resolution time-lapse imaging and lineage analysis, we are now in a position of great potential, allowing us to resolve heart formation at previously impossible levels of detail. Understanding how this essential organ forms not only addresses questions of fundamental biological significance but also provides a blueprint for strategies to both treat and model heart disease.

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Multiomic analysis reveals developmental dynamics of the human heart in health and disease

Cranley,

Kanemaru,

Bayraktar

et al. 2024

Preprint

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Developmental dynamics encompass both the specification of cell types and their spatial organisation into multicellular niches. Here we harness the power of single-cell and spatial multiomics to unravel embryonic and foetal cardiac tissue niches, which lead to the development of a new tool, TissueTypist. We infer developmental cell trajectories, including evidence for lineage relationships based on shared somatic mutations, within first- and second-trimester human hearts. We reveal that cardiac-resident macrophages likely originate from the yolk sac, forming heterogeneous subsets. CX3CR1+ macrophages with a microglia-like profile localise in the sinoatrial node, which may contribute to axon guidance for the innervating autonomic neurons. Foetal pacemaker cells exhibit distinct characteristics compared to their adult counterparts, including the expression of genes that are known to promote parasympathetic innervation. By comparing somatic mutation profiles of cardiomyocytes, we identify an early branching point where pacemaker cells diverge from working cardiomyocytes. We highlight the enhancer-mediated gene regulatory networks governing atrial and ventricular cardiomyocyte specification. The maturation of atrial cardiomyocytes into distinct left and right phenotypes, driven by transcription factors linked to atrial septal defect genes, underscores the significance of this process for healthy heart development. In the ventricle, cellular and transcriptional gradients along both pseudotime and the transmural axis provide a new molecular understanding of myocardial compaction. Finally, generating data from Trisomy 21 hearts and comparing this with the euploid atlas, we reveal a reduced abundance of specific cell types including compact cardiomyocytes. Overall, this extensive dataset and our precomputed models will form a valuable resource for the field.

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When Does the Human Embryonic Heart Start Beating? A Review of Contemporary and Historical Sources of Knowledge About the Onset of Blood Circulation in Man

Cited by 5 publications

References 73 publications

A patterned human heart tube organoid model generated by pluripotent stem cell self-assembly

A patterned human heart tube organoid model generated by pluripotent stem cell self-assembly

Formation of the Heart: Defining Cardiomyocyte Progenitors at Single-Cell Resolution

Multiomic analysis reveals developmental dynamics of the human heart in health and disease

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