Human induced pluripotent stem cell
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9561 | GEO | 2007/11/22
SECONDARY ACCESSION(S): PRJNA103377
REPOSITORIES: GEO
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Project description:The expression of four transcription factors (OCT3/4, SOX2, KLF4, and c-MYC) can reprogram mouse as well as human somatic cells to induced pluripotent stem (iPS) cells. Expression of the c-MYC, also known as an oncogene, might induce carcinogenesis and thus, iPS cells produced with the use of c-MYC transduction cannot be used for human therapeutic applications. Furthermore, reprogramming efficiency was significantly reduced in the absence of c-MYC transduction. Here, we generated iPS cells from mesenchymal stromal cells (MSCs) derived from human third molars (wisdom teeth) by retroviral transduction of OCT3/4, SOX2, and KLF4 without c-MYC. Interestingly, clonally expanded MSCs, named 10F-15, could be used for iPS cell generation with 100-fold higher efficiency compared to that of other clonally expanded MSCs and human dermal fibroblasts. These iPS cells resembled human embryonic stem (ES) cells in many aspects, including morphology, ES markers expression, global gene expression, epigenetic states, and the ability to differentiate into the three germ layers in vitro and in vivo. Because human third molars are discarded as clinical waste, our data indicate that MSCs isolated from human third molars are a valuable cell source for the generation of iPS cells.
2010-06-26 | GSE16963 | GEO
Project description:We have previously shown that pluripotent stem cells are induced from mouse fibroblasts by retroviral introduction of Oct3/4, Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 expression. These iPS (induced pluripotent stem) cells are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation. Fbx15-iPS cells, however, are different in gene expression and DNA methylation patterns and fail to produce adult chimeras. Here we show that selection for Nanog results in germ-line competent iPS cells, with more ES cell-like gene expression and DNA methylation patterns. The four transgenes were strongly silenced. We obtained adult chimeras from seven Nanog-iPS clones, with one clone transmitted through the germ-line to the next generation. Approximately 20% of the offspring developed tumors, where c-Myc transgene was reactivated. Thus iPS cells competent for germ-line chimeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application. Keywords: cell type comparison
2007-06-07 | GSE7841 | GEO
Project description:Reprogramming of somatic cells provides potential for the generation of specific cell types, which could be a key step in the study and treatment of human diseases. In vitro reprogramming of somatic cells into a pluripotent embryonic stem (ES) cellM-bM-^@M-^Slike state has been reported by retroviral transduction of murine fibroblasts using four embryonic transcription factors or through cell fusion of somatic and pluripotent stem cells. The generation of reprogrammed pluripotent cells using a somatic cell donor source such as bone marrow (BM) or peripheral blood is of particular therapeutic interest because of the relative ease of harvesting these cell types. Here we show that mouse adult BM mononuclear cellsM-oM-<M-^HBM MNCsM-oM-<M-^Iare competent as donor cells and can be reprogrammed into pluripotent ES cell-like cells. We isolated BM MNCs and embryonic fibroblasts (MEFs) from Oct4-EGFP transgenic mice, fused them with ES cells and infected them with retroviruses expressing Oct4, Sox2, Klf4, and c-Myc. Fused BM cells formed more ES-like colonies than did MEFs. Infected BM cells gave rise to iPS cells, although transduction efficiencies were not high. It was more efficient to pick up iPS colonies as compared with MEFs. BM-derived iPS (BM iPS) cells expressed embryonic stem cell markers, formed teratomas, and contributed to chimera mice with germline development. Clonal analysis revealed that BM iPS clones had diversity, although some clones were found to be genetically identical with different phenotypes. Here we demonstrate, for the first time, the induction of pluripotent cells directly from hematopoietic tissue. Gene expression profiling was performed in mouse BMMNCs, ES and BMMNC derived iPS cell lines.
2009-07-02 | E-GEOD-15775 | biostudies-arrayexpress
Project description:Induction of germline-competent pluripotent stem cells from mouse fibroblasts has been achieved by the ectopic expression of four genes (Oct3/4, Sox2, c-Myc and Klf4). If this method can be applied to humans for the generation of personalized human pluripotent stem cells, it would greatly facilitate the therapeutic application of stem cells by avoiding the problem of immune rejection by the recipient associated with allograft transplants. Here we show that the ectopic expression of the same four genes in human neonatal skin derived cells is sufficient to induce pluripotent stem cells indistinguishable from human embryonic stem cells in morphology, gene expression, DNA methylation, teratoma formation and long term self-renewal ability. Extensive analysis of colonies generated by ectopic expression of these four genes indicates the presence of considerable heterogeneity in the induced colonies. These results provide a new finding to generate human induced pluripotent stem cells from postnatal somatic tissues. Keywords: Cell type comparison
2008-03-16 | GSE9709 | GEO
Project description:The ectopic expression of a defined set of transcription factors, Oct4, Klf4, Sox2, and c-Myc, reprograms mouse embryonic fibroblasts (MEFs) and adult tail-tip fibroblasts (TTFs) into embryonic stem (ES)-like cells called induced pluripotent stem (iPS) cells. iPS cells have been generated from a variety of somatic cells, including embryonic and adult dermal fibroblasts, epithelial cells of the liver and stomach, pancreatic b cells, mature B lymphocytes, and adult neural stem cells (NSCs). While these studies demonstrated that most somatic cells are capable of acquiring pluripotency with minimal gene transduction, the poor efficiency of cell reprogramming and the uneven quality of iPS cells are still important problems. In particular, the choice of cell type most suitable for inducing high-quality iPS cells remains unclear. Here, we generated iPS cells from PDGFRa+ Sca-1+ (PaS) cells that represent highly enriched adult mouse mesenchymal stem cells (MSCs) and PDGFRa- Sca-1- osteo-progenitor (OP) cells. When we compared the induction efficiency and quality of individual iPS clones, MSCs had a higher reprogramming efficiency compared with OP cells and TTFs. The iPS cells induced from MSCs by Oct3/4, Sox2, and Klf4 appeared to be the closest equivalent to ES cells by DNA microarray gene profile and germline-transmission efficiency. We conclude that prospectively isolated MSCs are a promising candidate for the efficient and stable generation of high-quality iPS cells.
2010-08-21 | GSE23717 | GEO
Project description:Reprogramming of somatic cells provides potential for the generation of specific cell types, which could be a key step in the study and treatment of human diseases. In vitro reprogramming of somatic cells into a pluripotent embryonic stem (ES) cell–like state has been reported by retroviral transduction of murine fibroblasts using four embryonic transcription factors or through cell fusion of somatic and pluripotent stem cells. The generation of reprogrammed pluripotent cells using a somatic cell donor source such as bone marrow (BM) or peripheral blood is of particular therapeutic interest because of the relative ease of harvesting these cell types. Here we show that mouse adult BM mononuclear cells（BM MNCs）are competent as donor cells and can be reprogrammed into pluripotent ES cell-like cells. We isolated BM MNCs and embryonic fibroblasts (MEFs) from Oct4-EGFP transgenic mice, fused them with ES cells and infected them with retroviruses expressing Oct4, Sox2, Klf4, and c-Myc. Fused BM cells formed more ES-like colonies than did MEFs. Infected BM cells gave rise to iPS cells, although transduction efficiencies were not high. It was more efficient to pick up iPS colonies as compared with MEFs. BM-derived iPS (BM iPS) cells expressed embryonic stem cell markers, formed teratomas, and contributed to chimera mice with germline development. Clonal analysis revealed that BM iPS clones had diversity, although some clones were found to be genetically identical with different phenotypes. Here we demonstrate, for the first time, the induction of pluripotent cells directly from hematopoietic tissue.
2009-07-02 | GSE15775 | GEO
Project description:Human induced pluripotent stem (iPS) cells have the potential to establish a new field of promising regenerative medicine. Therefore, the safety and the efficiency of iPS-derived cells must be tested rigorously using appropriate animal models before human trials can commence. Here, we report the establishment of rabbit iPS cells as the first human-type iPS cells generated from a small laboratory animal species. Using lentiviral vectors, four human reprogramming genes (c-MYC, KLF4, SOX2 and OCT3/4) were introduced successfully into adult rabbit liver and stomach cells. The resulting rabbit iPS cells closely resembled human iPS cells; they formed flattened colonies with sharp edges and proliferated indefinitely in the presence of bFGF. They expressed the endogenous pluripotency markers c-MYC, KLF4, SOX2, OCT3/4 and NANOG, while the introduced human genes were completely silenced. Using in vitro differentiating conditions, rabbit iPS cells readily differentiated into ectoderm, mesoderm and endoderm. They also formed teratomas containing a variety of tissues of all three germ layers in immunodeficient mice. Thus, the rabbit iPS cells fulfilled all of the requirements for the acquisition of the fully reprogrammed state, showing high similarity to their embryonic stem (ES) cell counterparts we generated recently. However, their global gene expression analysis revealed a slight, but rigid difference between these two types of rabbit pluripotent stem cells. The rabbit model should enable us to compare iPS cells and ES cells under the same standardized conditions in evaluating their ultimate feasibility for pluripotent cell-based regenerative medicine in humans. Comparison of rabbit embryonic stem cells, rabbit somatic cells, and rabbit induced pluripotent stem cells at several timing (passage number 6, 7, 22, 23) of cultures. Eight samples were used for assessment.
2010-07-28 | E-GEOD-23190 | biostudies-arrayexpress
Project description:Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of the four transcription factors (OCT4, SOX2, c-MYC, KLF4). We previously reported that Oct4 alone is sufficient to directly reprogram adult mouse neural stem cells (NSCs) to iPS cells. Here, we report the generation of one-factor (1F) human iPS from human NSCs (1F hNiPS) by ectopic expression of Oct4 alone. 1F hNiPS cells resemble human embryonic stem cells (hESCs) in global gene expression profiles, epigenetic status and pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human NSCs to pluripotency. 1F iPS cell generation will accelerate this field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.
2009-09-23 | GSE15355 | GEO
Project description:It has been shown that DNA demethylation has a pivotal role in the generation of induced pluripotent stem (iPS) cells. However, the underlying mechanism is still unclear. Previous reports indicated that activation-induced cytidine deaminase (Aid) is involved in DNA demethylation in several developmental processes and cell fusion-mediated reprogramming. Based on the reports, we hypothesized that Aid may be involved in DNA demethylation during the iPS cell generation. In this study, we examined the function of Aid in iPS cell generation using Aid knockout (Aid-/-) mice expressing a GFP reporter under the control of a pluripotent stem cell marker, Nanog. By the introduction of Oct3/4, Sox2, Klf4 and c-Myc, Nanog-GFP positive iPS cells could be generated from the fibroblasts and primary B cells of Aid-/- mice. The Aid-/- iPS cells showed normal proliferation and gave rise to chimeras, indicating their capacity for self-renewal and pluripotency. The comprehensive DNA methylation analysis by MBD-sequening demonstrated that there were only a few differences between Aid+/+ and Aid-/- iPS cells. Aid+/+ and Aid-/- iPS colonies were generated from Aid+/+ and Aid-/- MEFs and picked up mechanically. The clones were passaged four times on feeder cells and two times on gelatin-coated dishes to exclude the contamination of feeder cells. Subsequently, the genome was isolated. Four Aid+/+ iPS cell clones and four Aid-/- iPS cell clones were compared. To confirm the validity of MBD-sequencing, four Aid+/+ iPS cell clones were compared with three ES cell clones or three Aid+/+ MEFs.
2014-04-10 | E-GEOD-52136 | biostudies-arrayexpress
Project description:Induced pluripotent stem (iPS) cells can be generated from somatic cells by transduction with several transcription factors in both mouse and human. However, direct reprogramming in other species has not been reported. Here, we established an efficient method to generate monkey iPS cells from fibroblasts by retrovirus-mediated introduction of the four monkey transcription factors OCT4 (POU5F1), SOX2, KLF4, and c-MYC. The monkey iPS cells displayed ES-like morphology, expressed ES cell-marker genes, shared similar global gene profiles and methylation status in the OCT4 promoter to those of monkey ES cells, and possessed the ability to differentiate into three germ layers in vitro and in vivo. Our results suggest that the mechanism of direct reprogramming is conserved among species. The efficient generation of monkey iPS cells will allow investigation of the feasibility of therapeutic cloning in primate model with various diseases. Keywords: Induced pluripotent stem, iPS, Rhesus monkey We analysed each sample (Rhesus monkey fibroblast, embryonic stem cell (ES) and induced pluripotent stem cell (iPS)) for three replications and sought to see high similarty between iPS and ES.
2010-05-15 | E-GEOD-13146 | biostudies-arrayexpress