Project description:Generation of in vitro models of cancer stem cells for in vivo xenograft models. hiPSC differentiation into a desired tissue allows studying physiologic processes in human-relevantcell systems. By introducing disease-specific mutations, these cells allow studying genetic origins of diseases in a tissue-specific manner.
Project description:Generation of in vitro models of cancer stem cells for in vivo xenograft models. hiPSC differentiation into a desired tissue allows studying physiologic processes in human-relevantcell systems. By introducing disease-specific mutations, these cells allow studying genetic origins of diseases in a tissue-specific manner.
Project description:Generation of in vitro models of cancer stem cells for in vivo xenograft models. hiPSC differentiation into a desired tissue allows studying physiologic processes in human-relevantcell systems. By introducing disease-specific mutations, these cells allow studying genetic origins of diseases in a tissue-specific manner.
Project description:Whereas highly penetrant variants have proven well-suited to human induced pluripotent stem cell (hiPSC)-based models, the power of hiPSC-based studies to resolve the much smaller effects of common variants within the size of cohorts that can be realistically assembled remains uncertain. In developing a large case/control schizophrenia (SZ) hiPSC-derived cohort of neural progenitor cells and neurons, we identified and accounted for a variety of technical and biological sources of variation. Reducing the stochastic effects of the differentiation process by correcting for cell type composition boosted the SZ signal in hiPSC-based models and increased the concordance with post mortem datasets. Because this concordance was strongest in hiPSC-neurons, it suggests that this cell type may better model genetic risk for SZ. We predict a growing convergence between hiPSC and post mortem studies as both approaches expand to larger cohort sizes. For studies of complex genetic disorders, to maximize the power of hiPSC cohorts currently feasible, in most cases and whenever possible, we recommend expanding the number of individuals even at the expense of the number of replicate hiPSC clones.