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The mammals and birds have four chambered hearts. The current models show the majority of myocardial cells derive from the first and second heart field, however, little is known regarding how heart field subpopulations contribute to specific regions in the heart. In this study, we revealed that the early -positive population in the inflow tract region contributes to the chamber myocardium by mouse-chick chimera and CreERT2/loxP lineage tracing system.

Bradycardia causes slow heart beating, which has high risk for heart failure or stroke. The only available treatment for bradycardia is implantation of electronic pacemakers. However, this treatment for bradycardia has several shortcomings: requirement of operation for implantation and for exchange of battery and the lack of response to autonomic nerve regulation. The purpose of this study was to develop a biological pacemaker, which could be used for replacement of electronic pacemakers.

Heart malformations are the most common type of birth defect, affecting more than 2 % of newborns and causing significant morbidity and mortality. In the past two decades, studies have revealed the function and importance of cardiac transcription factors during heart development and in congenital heart disease. Transcription factors generally form complexes with other transcription factors and/or with chromatin factors to perform specific functions. This review focuses on how chromatin factors modify cardiac transcription factors during cardiovascular development and disease.

Polycomb-group (PcG) proteins maintain transcriptional silencing through specific histone modification and are essential for cell-fate transition and proper development of embryonic and adult stem cells. Recent advances in molecular analysis of PcG proteins have revealed that the distinct subunit composition of PRC1 confers specific and nonoverlapping functions for regulation of embryonic and adult stem cells. Here, we provide an overview of recent findings regarding the role of PcG proteins in cardiac development, with focus on the diversity of PcG complexes.

For decades, it has been recognized that proteins, which are encoded by our genomes via transcription and translation, are building blocks that play vital roles in almost all biological processes. Mutations identified in many protein-coding genes are linked to various human diseases. However, this “protein-centered” dogma has been challenged in recent years with the discovery that majority of our genome is “noncoding” yet transcribed. Noncoding RNA has become the focus of “next generation” biology. Here, we review the emerging field of noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), and their function in cardiovascular biology and disease.

Congenital heart disease (CHD) is the most common cause of neonatal mortality related to birth defects. Etiology is multifactorial including genetic and/or environmental causes. The genetic etiology is known in less than 20 % cases. Animal studies have identified genes involved in cardiac development. However, generating cardiac phenotypes usually requires complete gene knockdown in animal models which does not reflect the haplo-insufficient model commonly seen in human CHD. Human pluripotent stem cells which include human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC) provide a unique in vitro platform to study human “disease in a dish” by providing a renewable resource of cells that can be differentiated into virtually any somatic cell type in the body. This chapter will discuss the use of human pluripotent stem cells to model human CHD.

The translation of in vitro engineered cardiac tissues (ECTs) from immature cardiac and stem cell-derived cells toward clinical therapies is benefiting from the following major advances: (1) rapid progress in the generation of immature cardiac cells from the cardiac and noncardiac cells of multiple species including normal and disease human cells, (2) incorporation of multiple cell lineages into 3D tissues, (3) multiple scalable 3D formulations including injectable gels and implantable tissues, and (4) insights into the regulation of cardiomyocyte proliferation and functional maturation. These advances are based on insights gained from investigating the regulation of cardiac morphogenesis and adaptation. Our lab continues to explore this approach, including changes in gene expression that occur in response to mechanical loading and tyrosine kinase inhibition, the incorporation of vascular fragments into ECTs, and the fabrication of porous implantable electrical sensors for in vitro conditioning and postimplantation testing. Significant challenges remain including optimizing ECT survival postimplantation and limited evidence of ECT functional coupling to the recipient myocardium. One clear focus of current research is the optimization and expansion of the cellular constituents, including CM, required for clinical-grade ECTs. Another major area of investigation will be large animal preclinical models that more accurately represent human CV failure and that can generate data in support of regulatory approval for phase I human clinical trials. The generation of reproducible human ECTs creates the opportunity to develop in vitro myocardial surrogate tissues for novel drug therapeutics and toxicity assays.

The genetic background of hypoplastic left heart syndrome (HLHS) is still unknown. Cardiac differentiation from pluripotent stem cells (PSCs) can recapitulate the cardiogenesis in vitro, and PSC technology could be useful to dissect the diseases with the complex mechanisms. In the past few years, some researches were reported to seek the pathogenesis of HLHS by using PSCs. This paper reports the achievements.

Pompe disease is an inherited neuromuscular disorder caused by a genetic deficiency of acid-glucosidase-alpha (GAA). The clinical symptoms of Pompe disease include progressive weakness, respiratory failure, and ventricular hypertrophy. Enzyme replacement therapy has been shown to ameliorate these symptoms. Cardiomyocytes derived from patient/disease-specific iPS cells (iPS-CMs) have been used for pathophysiological analyses, drug screening, and cell therapy. Our research goal was to generate cardiomyocytes that can be differentiated from gene-corrected Pompe disease-specific iPS cells.

A c-Kit (CD117) is a well-known cell surface marker for adult somatic stem cells. We harvested c-Kit-positive cardiac stem cells (CSCs) from adult rat hearts by performing magnetic-activated cell sorting (MACS) and subjected them to long-term bulk culture more than 40 times. We made 11 attempts to obtain c-Kit-positive cells from adult (6–8-month-old) rats. Our initial expectation was of obtaining cells with homogenous cardiac phenotypes. However, each CSC bulk culture expressed varying degrees of the genes and cell surface markers belonging to cardiac and other mesenchymal lineages. The results suggested that these CSCs retained multiple developmental potential to some extent. Consequently, we investigated these CSCs in detail, hoping to establish the regeneration method by using c-Kit-positive cardiac cells [1–12].