All blood cells are derived from multipotent stem cells, the so-called hematopoietic stem cells (HSCs), that in adults reside in the bone marrow. Most types of blood cells also develop there, with... Show moreAll blood cells are derived from multipotent stem cells, the so-called hematopoietic stem cells (HSCs), that in adults reside in the bone marrow. Most types of blood cells also develop there, with the notable exception of T lymphocytes that develop in the thymus. For both HSCs and developing T cells, interactions with the surrounding microenvironment are critical in regulating maintenance, differentiation, apoptosis, and proliferation. Such specialized regulatory microenvironments are referred to as niches and provide both soluble factors as well as cell-cell interactions between niche component cells and blood cells. Two pathways that are critical for early T cell development in the thymic niche are Wnt and Notch signaling. These signals also play important but controversial roles in the HSC niche. Here, we review the differences and similarities between the thymic and hematopoietic niches, with particular focus on Wnt and Notch signals, as well as the latest insights into regulation of these developmentally important pathways. Show less
Cardiac development is characterized by a complex interplay of chemical, mechanical, and electrical forces, which together contribute to the proper formation of the heart muscle. In adult... Show moreCardiac development is characterized by a complex interplay of chemical, mechanical, and electrical forces, which together contribute to the proper formation of the heart muscle. In adult myocardium, cardiomyocytes are elongated, well-coupled by gap junctions, and organized in spatially well-defined muscle fibers. This specific tissue architecture affects electromechanical activation and global cardiac function. Since the adult heart has only limited capacity for repair after injury, a significant loss of myocardial tissue often leads to impaired cardiac function. Recent efforts to transplant autologous cells to counteract this cardiomyocyte loss have resulted in marginal functional improvement and no evidence of myocyte regeneration. In order to achieve durable therapeutic efficiency, the transplanted cells will need to not only be cardiomyogenic, but also functionally integrate with host myocardial tissue and thereby contribute to both structural and functional restoration. Show less
In recent years the differentiation efficiency of human embryonic stem cells (hESCs) to cardiomyocytes has improved considerably. In general, hESC-derived cardiomyocytes are formed in aggregates,... Show moreIn recent years the differentiation efficiency of human embryonic stem cells (hESCs) to cardiomyocytes has improved considerably. In general, hESC-derived cardiomyocytes are formed in aggregates, which require dissociation for follow-up experimental analyses and (clinical) applications. Here, we show that inhibition of the Rho-associated kinase (ROCK) by Y-27632 improved survival of dissociated hESC-derived differentiated cells. A maximum effect on cell survival was already observed within the first 24 hours. Hereafter, no further differences in the percentage of apoptotic and proliferating cells were observed with or without ROCK-inhibitor treatment. Improved survival was observed in both cardiomyocyte as well as non-cardiomyocyte cell populations. Viable cardiomyocytes were indicated by the appearance of beating, sarcomeric organization of cardiac-specific proteins, and fluorescence of a mitochondrion-selective dye. These results facilitate development of applications of hESC-derived cardiomyocytes in multiple research areas. Furthermore, these findings may be applied to other cell types differentiated from hESCs or other stem cells. Show less
The two therapeutic approaches currently most advanced in clinical trials for Duchenne muscular dystrophy are antisense-mediated exon skipping and forced read-through of premature stop codons.... Show moreThe two therapeutic approaches currently most advanced in clinical trials for Duchenne muscular dystrophy are antisense-mediated exon skipping and forced read-through of premature stop codons. Interestingly, these approaches target the gene product rather than the gene itself. This review will explain the rationale and current state of affairs of these approaches and will then discuss how these gene-derived therapies might also be applicable to other diseases. Show less
In this report we present data about the effect of the Rhizobium NodZ enzyme on zebrafish development. We injected zebrafish embryos with a plasmid expressing NodZ protein, and we confirmed that... Show moreIn this report we present data about the effect of the Rhizobium NodZ enzyme on zebrafish development. We injected zebrafish embryos with a plasmid expressing NodZ protein, and we confirmed that the enzyme is active and has chitin oligosaccharide fucosyltransferase (NodZ) activity in vitro. In addition, the embryos injected with the NodZ-expressing plasmid, but not with a control plasmid, showed malformations or bends in the tail, and in some cases shunted tail structures and fused somites. These results clearly indicate that the likely substrates for this enzyme, chitin oligosaccharides and free N-glycans, have essential functions during early vertebrate embryogenesis. Show less
Canters, G.W.; Egmond, J.; Schaafsma, T.J.; Chan, I.Y.; Dorp, W G.; Waals, J.H. van der 1973
