Project description:Human induced pluripotent stem cells (hiPSCs) have become an invaluable tool for studying molecular disease mechanisms on a human genetic background. They can be differentiated into different cell types, including cardiac myocytes. Here, we studied the remodeling of mitochondrial protein complexes of hiPSCs cultured under hypoxic versus normoxic conditions.
Project description:Human induced pluripotent stem cells (hiPSCs) have become an invaluable tool to study molecular disease mechanisms on a human genetic background as they can be differentiated in different cell types including cardiac myocytes. One major downside that has decelerated the research performed in hiPSCs is that during propagation of these cells, changes in the karyotype of these cells have been observed. Interestingly, when hiPSCs are being cultured under hypoxic conditions and not as commonly done under normoxic conditions, hiPSCs grow faster to confluency and also changes in the karyotype of these cells are less frequently observed.
Project description:The equivalency of human induced pluripotent stem cells (hiPSCs) with human embryonic stem cells (hESCs) remains controversial. Here, we devised a strategy to assess the contribution of clonal growth, reprogramming method and genetic background to transcriptional patterns in hESCs and hiPSCs. Surprisingly, transcriptional variation originating from two different genetic backgrounds was dominant over variation due to the reprogramming method or cell type of origin of pluripotent cell lines. Moreover, the few differences we detected between isogenic hESCs and hiPSCs neither predicted functional outcome, nor distinguished an independently derived, larger set of unmatched hESC/hiPSC lines. We conclude that hESCs and hiPSCs are transcriptionally and functionally highly similar and cannot be distinguished by a consistent gene expression signature. Our data further imply that genetic background variation is a major confounding factor for transcriptional comparisons of pluripotent cell lines, explaining some of the previously observed expression differences between unmatched hESCs and hiPSCs. Expression profiling of human embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and fibroblasts, mostly in triplicates.
Project description:We developed a strategy to generate cardiac progenitor cells from human induced pluripotent stem cells using a novel small molecule. mRNA-sequencing results showed different gene expression profile among undifferentiated human induced pluripotent stem cells(hiPSCs), DMSO and ISX-9 treated hiPSCs.In comparsion with DMSO treated cells or undifferentiated hiPSCs, ISX-9 upregulated the genes related to WNT and cytoskeleton remodeling and TGF-β signaling, which are involved in heart development and cardiac differentiation. In addition, the genes related to cardiac differentiation signaling pathways were upregulated by ISX-9 including development of PIP3 signaling in cardiomyocyte myocytes, muscle contraction and NF-AT hypertrophy signaling.
