Identification of genes involved in endothelial differentiation is of great interest for the understanding of the cellular and molecular mechanisms involved in the development of new blood vessels. Mouse embryonic stem (mES) cells serve as a potential source of endothelial cells for transcriptomic analysis. We isolated endothelial cells from 8‐days old embryoid bodies by immuno‐magnetic separation using platelet endothelial cell adhesion molecule‐1 (also known as CD31) expressed on both early and mature endothelial cells. CD31+ cells exhibit endothelial‐like behavior by being able to incorporate DiI‐labeled acetylated low‐density lipoprotein as well as form tubular structures on matrigel. Quantitative and semi‐quantitative PCR analysis further demonstrated the increased expression of endothelial transcripts. To ascertain the specific transcriptomic identity of the CD31+ cells, large‐scale microarray analysis was carried out. Comparative bioinformatic analysis reveals an enrichment of the gene ontology categories angiogenesis, blood vessel morphogenesis, vasculogenesis and blood coagulation in the CD31+ cell population. Based on the transcriptomic signatures of the CD31+ cells, we conclude that this ES cell‐derived population contains endothelial‐like cells expressing a mesodermal marker BMP2 and possess an angiogenic potential. The transcriptomic characterization of CD31+ cells enables an in vitro functional genomic model to identify genes required for angiogenesis.
Objective— We recently isolated and characterized endothelial-like CD31 + cells derived from mouse embryonic stem (mES) cells and identified their transcriptome. The main objective of this study was to determine the functional relevance of the transcripts of unknown function (TUF) for vasculature development. Methods and Results— We selected 2 TUFs of more than 27 to study their role for blood vessel development in zebrafish. Morpholino (MO) knockdown of the zebrafish orthologs of the first TUF (TUF1, mouse cDNA BC022623) showed disruption of the intersegmental vessels (ISV) at 2 days postfertilization as observed by live imaging of fli:EGFP -transgenic embryos. The morphants showed abnormal blood circulation, but no effect on hematopoiesis was observed as demonstrated by gata-1 in situ hybridizations. Because knockdown of TUF1 resulted in disruption of the ISV patterning we named the TUF1 somitovasculin. TUF2 has been identified as cDNA clone BC020535. The MO knockdown of TUF2 resulted in a phenotype with an enlarged heart and the embryos lacked circulation completely. Conclusion— We have shown the participation of a novel transcript (named somitovasculin) in circulatory vessel development. The combination of expression profiling in differentiating mES cells and the zebrafish model has the potential for rapid identification and functional characterization of TUFs.
The cardiovascular system is the first system that is developed in the embryo. The cardiovascular development is a complex process involving the coordination, differentiation, and interaction of distinct cell lineages to form the heart and the diverse array of arteries, veins, and capillaries required to supply oxygen and nutrients to all tissues. Embryonic stem cells have been proposed as an interesting model system to investigate molecular and cellular mechanisms involved in mammalian development. The present review is focused on extrinsic soluble factors, intrinsic transcription factors, receptors, signal transduction pathways, and genes regulating the development of cardiovascular system in vivo and in vitro. Special emphasis has been given to cardiovascular genomics including gene expression studies on the cardiovascular system under developmental and pathophysiological conditions.
Epidemiological studies have repeatedly demonstrated a correlation between nutrition, development and the severity of malignant and non-malignant proliferative diseases such as cancer and atherosclerosis. Therefore, the prevention of chronic proliferative diseases through dietary intervention is currently receiving considerable attention. Until now. much of the research is being focused on the cellular and molecular action mechanisms of dietary small molecules explaining their beneficial effects. Dietary chemicals may affect gene expression in several human diseases. However, significant progress has been made and several molecular action mechanisms have been proposed. Alteration of genetical pathways by nutrition, also called "Nutrigenomics", may offer a new approach for understanding the beneficial effects of dietary compounds on the development of severe polygenic diseases, such as cardiovascular disease, diabetes and hypertension. This review focuses on the nutritional genomics of dietary chemicals with a special emphasis on catechins. Catechins belong to the flavonoid family, which are polyphenolic compounds available in foods of plant origin. Several epidemiological studies have reported that consumption of flavonoids, and especially catechins might function as chemopreventive agents against cancer and cardiovascular diseases.
The cardiovascular system is the first system that is developed in the embryo.The cardiovascular development is a complex process involving the coordination, differentiation, and interaction of distinct cell lineages to form the heart and the diverse array of arteries, veins, and capillaries required to supply oxygen and nutrients to all tissues.Embryonic stem cells have been proposed as an interesting model system to investigate molecular and cellular mechanisms involved in mammalian development.The present review is focused on extrinsic soluble factors, intrinsic transcription factors, receptors, signal transduction pathways, and genes regulating the development of cardiovascular system in vivo and in vitro.Special emphasis has been given to cardiovascular genomics including gene expression studies on the cardiovascular system under developmental and pathophysiological conditions.