Cardiovascular development and survival require Mef2c function in the myocardial but not the endothelial lineage

Materna, Stefan C.; Sinha, Tanvi; Barnes, Ralston M.; Bueren, Kelly Lammerts van; Black, Brian L.

doi:10.1016/j.ydbio.2018.12.002

Cited by 45 publications

(38 citation statements)

References 47 publications

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“…The heart looping, chamber formation, and left to right asymmetry are under the control of cardiogenic plate expressing genes NKX2.5, GATA, HANDS, and TBX5 [77]. During early cardiac development, NKX2.5 [78] and MHC2A [79] genes are essential, and in later stages, MEF2 [80], HAND1, and HAND2 genes [81,82] are actively transcribed. The regulation process during cardiac development is under the control of transcription factor genes GATA and TBX5, growth factors such as VEGF, FGF, and PDGF, and morphogenic proteins (BMP2, BMP4, BMP5) [79].…”

Section: Embryogenesis Of the Heartmentioning

confidence: 99%

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Suluba

Liu

Xia

et al. 2020

Egypt J Med Hum Genet

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Background: Congenital heart diseases (CHDs) are the most common congenital anomalies with an estimated prevalence of 8 in 1000 live births. CHDs occur as a result of abnormal embryogenesis of the heart. Congenital heart diseases are associated with significant mortality and morbidity. The damage of the heart is irreversible due to a lack of regeneration potential, and usually, the patients may require surgical intervention. Studying the developmental biology of the heart is essential not only in understanding the mechanisms and pathogenesis of congenital heart diseases but also in providing us with insight towards developing new preventive and treatment methods. Main body: The etiology of congenital heart diseases is still elusive. Both genetic and environmental factors have been implicated to play a role in the pathogenesis of the diseases. Recently, cardiac transcription factors, cardiacspecific genes, and signaling pathways, which are responsible for early cardiac morphogenesis have been extensively studied in both human and animal experiments but leave much to be desired. The discovery of novel genetic methods such as next generation sequencing and chromosomal microarrays have led to further study the genes, non-coding RNAs and subtle chromosomal changes, elucidating their implications to the etiology of congenital heart diseases. Studies have also implicated non-hereditary risk factors such as rubella infection, teratogens, maternal age, diabetes mellitus, and abnormal hemodynamics in causing CHDs. These etiological factors raise questions on multifactorial etiology of CHDs. It is therefore important to endeavor in research based on finding the causes of CHDs. Finding causative factors will enable us to plan intervention strategies and mitigate the consequences associated with CHDs. This review, therefore, puts forward the genetic and non-genetic causes of congenital heart diseases. Besides, it discusses crucial signaling pathways which are involved in early cardiac morphogenesis. Consequently, we aim to consolidate our knowledge on multifactorial causes of CHDs so as to pave a way for further research regarding CHDs. Conclusion: The multifactorial etiology of congenital heart diseases gives us a challenge to explicitly establishing specific causative factors and therefore plan intervention strategies. More well-designed studies and the use of novel genetic technologies could be the way through the discovery of etiological factors implicated in the pathogenesis of congenital heart diseases.

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Section: Embryogenesis Of the Heartmentioning

confidence: 99%

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Suluba

Liu

Xia

et al. 2020

Egypt J Med Hum Genet

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“…Augmented expression of several other genes associated with heart development [30][31][32][33][34]50,51 such as SOX4, MEFC2, RAMP2, CALCRL, and APLNR and organotypic cardiac endothelial cell genes 28 , such as HAPLN1, SPRX1 and IL6ST, was observed in coculture hiPS-ECs. Many of the coculture induced genes are also known to contribute to vascular development and angiogenesis, likely reflecting their response to angiogenic factors produced by cardiomyocytes.…”

Section: Discussionmentioning

confidence: 95%

“…A gene ontology classification analysis of the 130 genes upregulated in hiPS-ECs in both cell lines revealed activation of pathways associated with cardiovascular development, cell signaling, angiogenesis, and cell differentiation ( Figure 4A). More specifically, upregulation of general EC genes ( Figure 2D), and, interestingly, cardiac EC-specific genes 28 ( Figure 4B), as well as several genes associated with heart development [29][30][31][32][33][34] (Figure 4C), and angiogenesis [35][36][37] (Figure 4D) were observed in hiPS-ECs cultured together with hiPS-CMs. The respective data for the HEL24.3 cell line are presented in Figure V in the Data Supplement.…”

Section: The Data Supplement)mentioning

confidence: 94%

Modeling cellular crosstalk and organotypic vasculature development with human iPSC-derived endothelial cells and cardiomyocytes

Helle

Ampuja

Dainis

et al. 2020

Preprint

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RationaleCell-cell interactions are crucial for the development and function of the organs. Endothelial cells act as essential regulators of tissue growth and regeneration. In the heart, endothelial cells engage in delicate bidirectional communication with cardiomyocytes. The mechanisms and mediators of this crosstalk are still poorly known. Furthermore, endothelial cells in vivo are exposed to blood flow and their phenotype is greatly affected by shear stress. ObjectiveWe aimed to elucidate how cardiomyocytes regulate the development of organotypic phenotype in endothelial cells. In addition, the effects of flow-induced shear stress on endothelial cell phenotype were studied. Methods and resultsHuman induced pluripotent stem cell (hiPSC) -derived cardiomyocytes and endothelial cells were grown either as a monoculture or as a coculture. hiPS-endothelial cells were exposed to flow using the Ibidi-pump system. Single-cell RNA sequencing was performed to define cell populations and to uncover the effects on their transcriptomic phenotypes. The hiPS-cardiomyocyte differentiation resulted in two distinct populations; atrial and ventricular. Coculture had a more pronounced effect on hiPS-endothelial cells compared to hiPS-cardiomyocytes. Coculture increased hiPS-endothelial cell expression of transcripts related to vascular development and maturation, cardiac development, and the expression of cardiac endothelial cell -specific genes. Exposure to flow significantly reprogrammed the hiPS-endothelial cell transcriptome, and surprisingly, promoted the appearance of both venous and arterial clusters. ConclusionsSingle-cell RNA sequencing revealed distinct atrial and ventricular cell populations in hiPScardiomyocytes, and arterial and venous-like cell populations in flow exposed hiPS-endothelial cells. hiPS-endothelial cells acquired cardiac endothelial cell identity in coculture. Our study demonstrated that hiPS-cardiomoycytes and hiPS-endothelial cells readily adapt to coculture and flow in a consistent and relevant manner, indicating that the methods used represent improved physiological cell culturing conditions that potentially are more relevant in disease modelling. In addition, novel cardiomyocyte-endothelial cell crosstalk mediators were revealed.

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“…4A, the DEG, like MEF2C was highly expressed in hCPCs. MEF2C, as a marker of CPCs, plays a key role in the development of second heart field, and deletion of MEF2C could lead to failure of cardiac looping and cardiomyocyte formation [24,29]. This provides theoretical insights into the different manifestations of clinical structural heart diseases.…”

Section: Discussionmentioning

confidence: 99%

Dynamic transcriptome profiling toward understanding the development of the human embryonic heart during different Carnegie stages

et al. 2020

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Transcriptional regulation participates in heart development. However, the transcriptomes of human embryonic hearts during Carnegie stage (CS)10-CS16 have not been elucidated. Here, we found marked changes in the morphology and transcriptome of the human embryonic heart from CS10 to CS11. At CS12-CS14, the embryonic heart undergoes hypoxia-to-aerobic transformation. At CS14-CS16, transcriptome functions were related to energy metabolism, regulation of cholesterol, and processes related to inorganic substances. Moreover, the transcriptomes of cardiac progenitor cells derived from human embryonic stem cells (hESCs) most overlapped with those of human embryonic hearts at CS10. Cardiomyocytes derived from hESCs considerably overlapped with embryonic hearts at CS14-CS16. Overall, these results provide a new perspective into the characteristics of human embryonic heart development.

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Cardiovascular development and survival require Mef2c function in the myocardial but not the endothelial lineage

Cited by 45 publications

References 47 publications

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Modeling cellular crosstalk and organotypic vasculature development with human iPSC-derived endothelial cells and cardiomyocytes

Dynamic transcriptome profiling toward understanding the development of the human embryonic heart during different Carnegie stages

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