ABSTRACT Somites (SMs) comprise a transient stem cell population that gives rise to multiple cell types, including dermatome (D), myotome (MYO), sclerotome (SCL) and syndetome (SYN) cells. Although several groups have reported induction protocols for MYO and SCL from pluripotent stem cells, no studies have demonstrated the induction of SYN and D from SMs. Here, we report systematic induction of these cells from human induced pluripotent stem cells (iPSCs) under chemically defined conditions. We also successfully induced cells with differentiation capacities similar to those of multipotent mesenchymal stromal cells (MSC-like cells) from SMs. To evaluate the usefulness of these protocols, we conducted disease modeling of fibrodysplasia ossificans progressiva (FOP), an inherited disease that is characterized by heterotopic endochondral ossification in soft tissues after birth. Importantly, FOP-iPSC-derived MSC-like cells showed enhanced chondrogenesis, whereas FOP-iPSC-derived SCL did not, possibly recapitulating normal embryonic skeletogenesis in FOP and cell-type specificity of FOP phenotypes. These results demonstrate the usefulness of multipotent SMs for disease modeling and future cell-based therapies.
Additional file 12 Table S6. Datasets and performances of 3D structure reconstructions with highly variable genes selected by Seurat (score = accuracy + ARI).
Circulating endothelial progenitor cells (EPCs) are believed to home to sites of neovascularization, contributing to vascular regeneration either directly via incorporation into newly forming vascular structures or indirectly via the secretion of pro-angiogenic growth factors, thereby enhancing the overall vascular and hemodynamic recovery of ischemic tissues. The therapeutic application of EPCs has been shown to be effective in animal models of ischemia, and we as well as other groups involved in clinical trials have demonstrated that the use of EPCs was safe and feasible for the treatment of critical limb ischemia and cardiovascular diseases. However, many issues in the field of EPC biology, especially in regard to the proper and unambiguous molecular characterization of these cells, still remain unresolved, hampering not only basic research but also the effective therapeutic use and widespread application of these cells. Further, recent evidence suggests that several diseases and pathological conditions are correlated with a reduction in the number and biological activity of EPCs, making the development of novel strategies to overcome the current limitations and shortcomings of this promising but still limited therapeutic tool by refinement and improvement of EPC purification, expansion, and administration techniques, a rather pressing issue. Antioxid. Redox Signal. 15, 949–965.
Recent advances in the identification and analysis of protein–protein interaction complexes associated with synapses and synaptic proteins deepened not only our insights into the molecular composition and dynamic structural makeup of interneuronal connections but contributed also significantly to our understanding of the molecular and mechanistic aspects underlying functional plasticity in neuronal networks. In particular proteome analytical tools, combining traditional isolation protocols with modern mass spectrometric approaches, were utilized successfully for the molecular analysis of chemical synapses and other neuronal subcellular structures revealing new and exciting insights into the temporal and spatial changes of the proteins composing or associated with for example synaptic vesicles, synaptic membranes, or postsynaptic densities (PSDs). Proteomic approaches may thus offer also a chance to gain valuable insights into the so far elusive molecular composition of electrical synapses, the Cinderella fated and long neglected little brethren of "classical" chemical synapses. In this chapter we provide an experimental basis of how such an analysis can be designed, with a major focus on the most abundant electrical synapse protein, connexin36.
In recent years, a diverse array of in vitro cell-derived models of mammalian development have been described that hold immense potential for exploring fundamental questions in developmental biology, particularly in the case of the human embryo where ethical and technical limitations restrict research. These models open up new avenues toward biomedical advances in in vitro fertilization, clinical research, and drug screening with potential to impact wider society across many diverse fields. These technologies raise challenging questions with profound ethical, regulatory, and social implications that deserve due consideration. Here, we discuss the potential impacts of embryo-like models, and their biomedical potential and current limitations.
