Whole Genome Sequencing of hiPS cells
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ABSTRACT:
PROVIDER: EGAS00001000008 | EGA |
REPOSITORIES: EGA
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Project description:Human induced pluripotent stem (hiPS) cells hold great promise for regenerative medicine. Safety issues of use of hiPS cells however remain to be addressed. One of such issues is mutations derived from somatic donor cells and introduced during genome manipulation. We sequence whole genomes of hiPS cells and analyzed mutations. Our study brings hiPS cell technology one step closer to application to regenerative medicine.
| EGAD00001000362 | EGA
Project description:To date, all methods to generate induced pluripotent stem (iPS) cells require the use of genetic materials and/or potentially mutagenic chemicals. Here we report the generation of stable human iPS cells from human fibroblasts by directly delivering defined reprogramming proteins. This system eliminates the potential risks associated with genetic and/or chemical manipulation, and could provide a safe and physiologically intact source of cells for regenerative medicine. Total RNAs were prepared from human fibroblasts, H9, and hiPS lines using TRIzol reagent (Invitrogen, Carlsbad, CA) and hybridized to Affymetrix Human Expression Array U133 Plus 2.0 analyzing over 47,000 human transcripts at the Harvard Partners Center for Genomics and Genetics. Detailed procedure is described in the website at http://www.hpcgg.org/Microarrays/overview.jsp
2009-05-29 | E-GEOD-16093 | biostudies-arrayexpress
Project description:Pluripotent stem cells, which are capable to generate any cell type of the human body, such as human embryonic stem cells (hESC) or human induced pluripotent stem cells (hiPS) are a very promising source of cells for regenerative medicine. However, the genesis, the in vitro amplification and the differentiation of these cells still need improvement before clinical use. This study aimed to improve our knowledge on these critical steps in pluripotent stem cell generation. We derived new hESC lines, generated hiPS and compared these cell types with human foreskin fibroblasts and partially reprogrammed fibroblasts.
2010-05-01 | GSE15491 | GEO
Project description:Mesenchymal stromal cells (MSCs) hold great promise in the field of liver regenerative medicine. However, the mechanisms and reversibility of hepatogenic differentiation in MSCs are poorly understood. Here, we demonstrate that hepatogenic differentiation of MSCs is a reversible process and is modulated by the transforming growth factor beta 1- DNA methyltransferases (TGF-β1-Dnmts) axis. Dnmt1 and Dnmt3a differentially regulate hepatogenic differentiation and de-differentiation in response to the alternation of TGF-β1 concentration. Knockdown of Dnmt1 accelerates the hepatogenic differentiation in MSCs-derived hepatocyte-like cells (dHeps) whereas Knockdown of Dnmt3a represses hepatogenic differentiation. Conclusions: Our finding first demonstrates that epigenetic regulation by Dnmts in response to stimulation from the surrounding microenvironment controls the reversibility of hepatogenic differentiation in MSCs. Manipulation of Dnmts provides a rapid and efficient differentiation protocol to generate functional dHeps from MSCs that may provide clinical potential for regenerative medicine.
2017-08-11 | GSE73762 | GEO
Project description:Mesenchymal stromal cells (MSCs) hold great promise in the field of liver regenerative medicine. However, the mechanisms and reversibility of hepatogenic differentiation in MSCs are poorly understood. Here, we demonstrate that hepatogenic differentiation of MSCs is a reversible process and is modulated by the transforming growth factor beta 1- DNA methyltransferases (TGF-β1-Dnmts) axis. Dnmt1 and Dnmt3a differentially regulate hepatogenic differentiation and de-differentiation in response to the alternation of TGF-β1 concentration. Knockdown of Dnmt1 accelerates the hepatogenic differentiation in MSCs-derived hepatocyte-like cells (dHeps) whereas Knockdown of Dnmt3a represses hepatogenic differentiation. Conclusions: Our finding first demonstrates that epigenetic regulation by Dnmts in response to stimulation from the surrounding microenvironment controls the reversibility of hepatogenic differentiation in MSCs. Manipulation of Dnmts provides a rapid and efficient differentiation protocol to generate functional dHeps from MSCs that may provide clinical potential for regenerative medicine.
2017-08-11 | GSE73617 | GEO
Project description:Pluripotent stem cells, which are capable to generate any cell type of the human body, such as human embryonic stem cells (hESC) or human induced pluripotent stem cells (hiPS) are a very promising source of cells for regenerative medicine. However, the genesis, the in vitro amplification and the differentiation of these cells still need improvement before clinical use. This study aimed to improve our knowledge on these critical steps in pluripotent stem cell generation. We derived new hESC lines, generated hiPS and compared these cell types with human foreskin fibroblasts and partially reprogrammed fibroblasts. We included in the overall study hESC, hiPS, human foreskin fibroblasts and partially reprogrammed fibroblasts. Here, hESC lines derived from embryos were hybridized on U133 Plus 2.0 GeneChips (Affymetrix). All samples were normalized using the MAS5 (GCOS 1.2) algorithm, using the default analysis settings and global scaling as normalization method, with a trimmed mean target intensity value (TGT) of each array arbitrarily set to 100. Human pluripotent stem cells were compared with somatic samples and partially reprogrammed cells.
2010-05-27 | E-GEOD-15491 | biostudies-arrayexpress
Project description:To date, all methods to generate induced pluripotent stem (iPS) cells require the use of genetic materials and/or potentially mutagenic chemicals. Here we report the generation of stable human iPS cells from human fibroblasts by directly delivering defined reprogramming proteins. This system eliminates the potential risks associated with genetic and/or chemical manipulation, and could provide a safe and physiologically intact source of cells for regenerative medicine.
2009-05-29 | GSE16093 | GEO
Project description:Cellular transitions hold great promise in translational medicine research. However, therapeutic applications are limited by the low efficiency and safety concerns of using transcription factors. Small molecules provide a temporal and highly tuneable approach to overcome these issues. Here, we present PC3T, a computational framework to identify enrich molecules that induce desired cellular transitions, and PC3T was able to consistently identify enrich small molecules that had been experimentally validated in both bulk and single cell datasets. We then predicted and experimentally validated small molecules reprogramming of fibroblasts into hepatocyte-like cells and found that the fibroblasts exhibited epithelial cell morphology and hepatocyte-like specific gene expression pattern after treatment.
2023-05-09 | GSE231967 | GEO
Project description:Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected mouse DMD-induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD-iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Remarkably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation, and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes.
2024-04-25 | GSE215061 | GEO
Project description:Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected mouse DMD-induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD-iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Remarkably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation, and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes.
2024-04-25 | GSE254371 | GEO