There is considerable evidence that differentiating cells are the most sensitive of all cells of the living organism. When embryos are x-irradiated at sublethal levels and subsequently studied histologically it is found that the regions showing the greatest radiation damage, as indicated by pycnotic nuclei, do not necessarily correspond with embryonic areas known to have a high mitotic index at...

Several studies have demonstrated a multiphasic role for Wnt signaling during embryonic cardiogenesis and developed protocols that enrich for cardiac derivatives during in vitro differentiation of human pluripotent stem cells (hPSCs). However, few studies have investigated the role of Wnt signaling in the specification of cardiac progenitor cells (CPCs) toward downstream fates. Using transgenic...

Ischemic heart diseases are a serious health problem worldwide. The transplantation of mesenchymal stem cells (MSCs) has been investigated in numerous clinical trials on various other diseases due to the self-renewal capacity of these cells and their potential to differentiate into a variety of cell types. The presence of excess reactive oxygen species in injured myocardium causes cardiac dysfu...

We have isolated a cDNA fragment encoding a portion of the myosin heavy chain alpha-isoform (XMHC alpha) in the amphibian, Xenopus laevis. The XMHC alpha transcript is highly enriched in adult heart RNA and is expressed exclusively in embryonic heart tissue. It therefore provides a tissue-specific marker for cardiac muscle differentiation during early embryogenesis. Using an RNAase protection a...

Failure of the directed differentiation of the transplanted stem cells into cardiomyocytes is still a major challenge of cardiac regeneration therapy. Our recent study has demonstrated that the expression of histone deacetylase 1 (HDAC1) is decreased in bone mesenchymal stem cells (BMSCs) during their differentiation into cardiomyocytes. However, the potential roles of HDAC1 in cardiac cell dif...

Retinoic acid (RA) has several established functions during cardiac development, including actions in the fetal epicardium required for myocardial growth. An open question is if retinoid effects are limited to growth factor stimulation pathway(s) or if additional actions on uncommitted progenitor/stem populations might drive cardiac differentiation. Here we report the dual effects of RA deficie...

Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that di...

Calreticulin is a Ca(2+)-binding molecular chaperone of the lumen of the endoplasmic reticulum. Calreticulin has been shown to be essential for cardiac and neural development in mice, but the mechanism by which it functions in cell differentiation is not fully understood. To examine the role of calreticulin in cardiac differentiation, the calreticulin gene was introduced into rat cardiomyoblast...

Results from lineage tracing studies indicate that precursor cells in the ventricles give rise to both cardiac muscle and conduction cells. Cardiac conduction cells are specialized cells responsible for orchestrating the rhythmic contractions of the heart. Here, we show that Notch signaling plays an important role in the differentiation of cardiac muscle and conduction cell lineages in the vent...

The fashioning of a vertebrate organ requires integration of decisions of cell fate by individual cells with those that regulate organotypic form. Logical candidates for this role, in an organ such as the heart, are genes that initiate the differentiation process leading to heart muscle and those that define the earliest embryonic heart field, but for neither class are genes defined. We cloned ...