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:proteomes of the Human Embryonic Kidney (HEK) cells, the human induced pluripotent stem cells (hiPSCs), and the human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
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.
Project description:The eye is an ideal target organ for Human induced pluripotent stem cells (hiPSCs)-based cellular therapies. However, the application of hiPSCs in ocular disease treatment is still challenging because the production of clinical-grade autologous hiPSCs via genetic techniques remains expensive, time-consuming, and subject to safety concerns. Addressing these challenges, our study utilized a recently reported chemical method to derive human chemically induced pluripotent stem cells (hCiPSCs), which simplified the reprogramming process by using small molecules, offering a more straightforward and potentially safer alternative to derive hiPSCs. Moreover, we demonstrate that hCiPSCs can be efficiently differentiated into functional retinal pigment epithelium (RPE) cells, showing promise for the treatment of age-related macular degeneration (AMD) and other retinal diseases. Our study provides a method for the efficient and safe production of autologous retinal cells, facilitating the advancement of personalized stem cell therapies for ocular diseases.
Project description:Differentiation of mammalian pluripotent cells involves large-scale changes in transcription and, among the molecules that orchestrate these changes, chromatin remodellers are essential to initiate, establish and maintain a new gene regulatory network. The NuRD complex is a highly conserved chromatin remodeller which fine-tunes gene expression in embryonic stem cells. While the function of NuRD in mouse pluripotent cells has been well defined, no study yet has defined NuRD function in human pluripotent cells. We investigated the structure and function of NuRD in human induced pluripotent stem cells (hiPSCs). Using immunoprecipitation followed by mass-spectrometry in hiPSCs and in naive or primed mouse pluripotent stem cells, we find that NuRD structure and biochemical interactors are generally conserved. Using RNA sequencing, we find that, whereas in mouse primed stem cells and in mouse naive ES cells, NuRD is required for an appropriate level of transcriptional response to differentiation signals, hiPSCs require NuRD to initiate these responses. This difference indicates that mouse and human cells interpret and respond to induction of differentiation differently.
