Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

Kokkinopoulos, Ioannis; Ishida, Hidekazu; Saba, Rie; Ruchaya, Prashant; Cabrera, Claudia; Struebig, Monika; Barnes, Michael R.; Terry, Anna; Kaneko, Masahiro; Shintani, Yasunori; Coppen, Steven R.; Shiratori, Hidetaka; Ameen, Torath; Mein, Charles A.; Hamada, Hiroshi; Suzuki, Ken; Yashiro, Kenta

doi:10.1371/journal.pone.0140831

Cited by 32 publications

(74 citation statements)

References 71 publications

(124 reference statements)

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“…It became clear that the primitive cardiac tube (Figure ) derives from the FHF and basically has a left ventricular identity. This identity prominently displays Tbx5 and Nkx2.5 expression in the mouse embryo . In the embryo, earlier cardiac crescent progenitors of the SHF are positioned medially to the FHF (Figure 3 Left).…”

Section: The First Heart Fieldmentioning

confidence: 93%

“…In ascidian embryos, cell fates are first restricted to a few progenitors, which are secondarily amplified (From Anderson and Christiaen 59 ) in the mouse embryo. 49 In the embryo, earlier cardiac crescent progenitors of the SHF are positioned medially to the FHF (Figure 3 Left). Embryological studies indicate that the FHF-derived left ventricle is ancestral, 24,50 with progenitor cells of the arterial and venous poles 48,51-54 positioned posteriorly to the ventricular field.…”

Section: The First Heart Fieldmentioning

confidence: 99%

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Development and evolution of the metazoan heart

Poelmann

Groot

2019

Developmental Dynamics

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The mechanisms of the evolution and development of the heart in metazoans are highlighted, starting with the evolutionary origin of the contractile cell, supposedly the precursor of cardiomyocytes. The last eukaryotic common ancestor is likely a combination of several cellular organisms containing their specific metabolic pathways and genetic signaling networks. During evolution, these tool kits diversified. Shared parts of these conserved tool kits act in the development and functioning of pumping hearts and open or closed circulations in such diverse species as arthropods, mollusks, and chordates. The genetic tool kits became more complex by gene duplications, addition of epigenetic modifications, influence of environmental factors, incorporation of viral genomes, cardiac changes necessitated by air‐breathing, and many others. We evaluate mechanisms involved in mollusks in the formation of three separate hearts and in arthropods in the formation of a tubular heart. A tubular heart is also present in embryonic stages of chordates, providing the septated four‐chambered heart, in birds and mammals passing through stages with first and second heart fields. The four‐chambered heart permits the formation of high‐pressure systemic and low‐pressure pulmonary circulation in birds and mammals, allowing for high metabolic rates and maintenance of body temperature. Crocodiles also have a (nearly) separated circulation, but their resting temperature conforms with the environment. We argue that endothermic ancestors lost the capacity to elevate their body temperature during evolution, resulting in ectothermic modern crocodilians. Finally, a clinically relevant paragraph reviews the occurrence of congenital cardiac malformations in humans as derailments of signaling pathways during embryonic development.

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Section: The First Heart Fieldmentioning

confidence: 93%

Section: The First Heart Fieldmentioning

confidence: 99%

Development and evolution of the metazoan heart

Poelmann

Groot

2019

Developmental Dynamics

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“…Sox17 Expression in CPCs. We previously performed single-cell gene expression profiling of mouse embryonic CPCs from the EB to early head fold (EHF) stage (23,24). We validated cell types based on the expression of marker genes including Sox2 for the epiblast or neural ectoderm, Sox17 for the endoderm or arterial endothelial cells (18,25), Cryptic (also known as Cfc1) for the lateral plate mesoderm (LPM), and Nkx2-5 or Tbx5 for CPCs (1,3).…”

Section: Resultsmentioning

confidence: 99%

Sox17expression in endocardium precursor cells regulates heart development in mice

Saba

Kitajima

Rainbow

et al. 2019

Preprint

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The endocardium is the endothelial component of the vertebrate heart and plays a key role in heart development. Cardiac progenitor cells (CPCs) that express the homeobox gene Nkx2-5 give rise to the endocardium. Where, when, and how the endocardium segregates during embryogenesis have remained largely unknown, however. We now show that Nkx2-5 + CPCs that express the Sry-type HMG box gene Sox17 specifically differentiate into the endocardium in mouse embryos. Approximately 20% to 30% of Nkx2-5 + CPCs transiently express Sox17 from embryonic day (E) 7.5 to E8.5.Although Sox17 is not essential or sufficient for endocardium fate, it can bias the fate of CPCs toward the endocardium. On the other hand, Sox17 expression in the endocardium is required for heart development. Deletion of Sox17 specifically in the mesoderm markedly impaired endocardium development with regard to cell proliferation and behavior. The proliferation of cardiomyocytes, ventricular trabeculation, and myocardium thickening were also impaired in a non-cellautonomous manner in the Sox17 mutant, resulting in anomalous morphology of the heart, likely as a consequence of down-regulation of NOTCH signaling. Changes in gene expression profile in both the endocardium and myocardium preceded the reduction in NOTCH-related gene expression in the mutant embryos, suggesting that Sox17 expression in the endocardium regulates an unknown signal required for nurturing of the myocardium. Our results thus provide insight into differentiation of the endocardium and its role in heart development. SignificanceThe endocardium is vital for vertebrate heart development; however, the molecular mechanisms regulating fate determination and differentiation remain largely unknown.Here, we show that a part of the earliest cardiac progenitor cells (CPCs) transiently and exclusively express Sry-type HMG box gene Sox17 in the mouse embryo. Sox17expressing CPCs specifically differentiate to the endocardium. Sox17 biases the fate of CPCs toward the endocardium, and regulates proliferation and cellular behavior cell autonomously. Conversely, Sox17 in the endocardium regulates the myocardium

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“…Trypsinisation itself likely damages differentiating cells and affects their viability. Indeed, cells that were subjected to a monolayer differentiation protocol has been shown to provide cells with increased survival posttransplantation, in comparison to poor engraftment of embryoid‐body‐derived cells, in rat infarcted hearts (Laflamme et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…We used a murine ES line that was originally made in our laboratory as described previously (Kokkinopoulos et al, 2015). In addition, E14tg2a was also used for the experiment.…”

Section: Differentiation Assaysmentioning

confidence: 99%

Cardiomyocyte differentiation from mouse embryonic stem cells using a simple and defined protocol

Kokkinopoulos

Ishida

Saba

et al. 2015

Developmental Dynamics

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Background: Embryonic stem (ES) cells are pluripotent cells with the ability to differentiate to any cell type of the resident organism. In recent years, significant advances have been made in using these cells to obtain large numbers of cardiomyocyte (CM) -like cells for scientific research and clinical application. A vast number of protocols have emerged describing differentiation methods without the use of animal serum or extracts restrictive for use in a human clinical setting. These techniques follow a complicated procedure, which although successful, show a relatively varied yield among cell batches. Results: We have designed a three-step differentiation protocol using defined reagents and a monolayer culture without feeder cells, avoiding embryoid body formation and multiple trypsin treatment, in which beating foci appeared as early as day 6 in in vitro differentiating conditions. Our results show a high yield of CM reaching approximately 60% of the differentiated cells after 13 days in vitro.

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Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

Cited by 32 publications

References 71 publications

Development and evolution of the metazoan heart

Development and evolution of the metazoan heart

Sox17expression in endocardium precursor cells regulates heart development in mice

Cardiomyocyte differentiation from mouse embryonic stem cells using a simple and defined protocol

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