Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA130349 | ENA |
REPOSITORIES: ENA
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Project description:Ectopic expression of four transcription factors including Oct4, Sox2, Klf4 and c-Myc in differentiated fibroblast cells could reset the cell fate of fibroblast cells to pluripotent state. Subsequently, fully pluripotency of these so-called induced pluripotent stem cells (iPSCs) has been demonstrated as viable mice could be generated autonomously from iPS cells through tetraploid blastocyst complementation. Moreover, the generation of human and patient-specific iPS cells have raised the possibility of utilizing iPS cells clinically. However, the utilization of c-Myc in iPS cells induction greatly increased the incidence of tumorigenecity in the iPS-chimeric mice and also might hinder the clinical application of human iPS cells in the future. Fortunately, c-Myc has been recently found dispensable for iPS induction even though the iPS induction efficiency is greatly reduced in the absence of c-Myc. However, it remains unknown if these three factors-induced iPS cells are fully pluripotent. In the present study, we have successfully demonstrated that 3-factor iPS cells could also be fully pluripotent as viable mice could be generated from 3-factor iPS cells autonomously via tetraploid complementation and moreover, our data indicated that the pluripotency regulatory mechanism in 3-factor iPS cells might be distinct from 4-factor iPS cells. We compared the gene expression profile of iPS cells with and without the tetraploid embryo complementation competence. Three biological repeats were included for each line.
2010-10-19 | E-GEOD-24046 | biostudies-arrayexpress
Project description:Ectopic expression of four transcription factors including Oct4, Sox2, Klf4 and c-Myc in differentiated fibroblast cells could reset the cell fate of fibroblast cells to pluripotent state. Subsequently, fully pluripotency of these so-called induced pluripotent stem cells (iPSCs) has been demonstrated as viable mice could be generated autonomously from iPS cells through tetraploid blastocyst complementation. Moreover, the generation of human and patient-specific iPS cells have raised the possibility of utilizing iPS cells clinically. However, the utilization of c-Myc in iPS cells induction greatly increased the incidence of tumorigenecity in the iPS-chimeric mice and also might hinder the clinical application of human iPS cells in the future. Fortunately, c-Myc has been recently found dispensable for iPS induction even though the iPS induction efficiency is greatly reduced in the absence of c-Myc. However, it remains unknown if these three factors-induced iPS cells are fully pluripotent. In the present study, we have successfully demonstrated that 3-factor iPS cells could also be fully pluripotent as viable mice could be generated from 3-factor iPS cells autonomously via tetraploid complementation and moreover, our data indicated that the pluripotency regulatory mechanism in 3-factor iPS cells might be distinct from 4-factor iPS cells.
2010-10-19 | GSE24046 | GEO
Project description:Differentiated somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by forced expression of four transcription factors—Oct4, Sox2, Klf4, and c-Myc. However, it remains undetermined whether the reprogrammed iPS cells are fully pluripotent, resembling normal embryonic stem (ES) cells, given that no iPS cell lines have been shown to possess the capability to autonomously generate full-term mice after injection into tetraploid blastocysts. Here, we provide evidence demonstrating that iPS cells induced by the four transcription factors can be fully pluripotent and that full-term mice can be produced from complemented tetraploid blastocysts. This work serves as a proof of principle that iPS cells can generate full term embryos by tetraploid complementation.
2009-07-09 | GSE17004 | GEO
Project description:Differentiated somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by forced expression of four transcription factorsâOct4, Sox2, Klf4, and c-Myc. However, it remains undetermined whether the reprogrammed iPS cells are fully pluripotent, resembling normal embryonic stem (ES) cells, given that no iPS cell lines have been shown to possess the capability to autonomously generate full-term mice after injection into tetraploid blastocysts. Here, we provide evidence demonstrating that iPS cells induced by the four transcription factors can be fully pluripotent and that full-term mice can be produced from complemented tetraploid blastocysts. This work serves as a proof of principle that iPS cells can generate full term embryos by tetraploid complementation. We compared the gene expression profile of iPS cell, ES cell and MEF. ES cell and MEF served as control for iPS cell. Three biological repeats were included for each line.
2010-08-18 | E-GEOD-17004 | biostudies-arrayexpress
Project description:Ten-eleven translocation (TET) family enzymes can convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) in DNA and have been proposed as potential DNA demethylase candidates1. Evidences from recent studies indicated that Tet1 is predominantly expressed in ES cells and plays dual functions in promoting transcription of pluripotency genes and as well as participating in the repression of developmental genes by facilitating recruitment of PRC21-5. These studies further raised the possibility that Tet1 might play a role in somatic cell reprogramming. Here, we provide evidence showing that Tet1 can substitute for pluripotent transcription factors in reprogramming differentiated somatic cells to pluripotent stem cells. Tet1 can replace any one of the four traditional transcription factors including Oct4, Sox2, Klf4 and c-Myc during somatic cell reprogramming. Subsequently, the chimeric mice with germline transmission capacity could be efficiently produced from all induced pluripotent stem (iPS) cell lines reprogrammed by OT (Oct4, Tet1), TSKM (Tet1, Sox2, Klf4, c-Myc), OTK, OTKM and OSTM combinations. Furthermore, the TSKM-reprogrammed iPS cells without using Oct4 could produce viable full-term iPS mice with normal fertility through tetraploid complementation and secondary iPS cells could be induced subsequently from the somatic cells retrieved from the iPS mice. Moreover, we demonstrated that conversion of 5mC into 5hmC in Nanog promoter occurred during reprogramming, which might account in part for the mechanism of Tet1 mediated reprogramming. To our knowledge, our study provides the first evidence demonstrating that DNA modifying enzyme Tet1 can replace the pluripotent transcription factors to reprogram differentiated somatic cells to iPS cells. Gene expression profile of iPS cells and ES cells were generated by Affymetrix Mouse Gene 1.0 ST Array. The Gene expression profile of ES cell R1 was used as control. Three biological repeats were included for each line.
2011-05-07 | E-GEOD-29102 | biostudies-arrayexpress
Project description:Full pluripotency of induced pluripotent stem (iPS) cells has been determined as viable all-iPS mice can be generated through tetraploid complementation. Subsequently, activation of imprinted Dlk-Dio3 gene cluster has been suggested to correlate with the pluripotency of iPS cells1. However, evidence from recent studies has demonstrated that loss of imprinting at the Dlk-Dio3 locus did not correlate strictly with the reduced pluripotency of iPS cells. Therefore, it becomes indispensable to exploit other reliable molecular markers for evaluating the quality of iPS cells accurately. In the present study, we successfully utilize the sequential reprogramming approach and produce all-iPS mice to six generations using iPS cell lines derived from different cell lineages which contain the same proviral integration in the genome. By comparing the global gene expression and epigenetic modifications of both "tetra-on" and corresponding "tetra-off" iPS cell lines established from either mesenchymal or hematopoietic lineages through deep sequencing analysis of mRNA expression, small RNA profiling, histone modifications (H3K4m2, H3K4me3 and H3K27me3) and DNA methylation, very few differences are detected among all the iPS cell lines investigated. However, we find that two imprinted genes, disruption of which correlate with the reduced pluripotency of iPS cells. Therefore, our data not only provide the first demonstration that producing of all-iPS mice to six generations is feasible, but reveal that two imprinted regions can be served as pluripotency markers of iPS cells. Examination of the mRNA expression in 13 cell types
2013-12-06 | E-GEOD-36290 | biostudies-arrayexpress
Project description:Full pluripotency of induced pluripotent stem (iPS) cells has been determined as viable all-iPS mice can be generated through tetraploid complementation. Subsequently, activation of imprinted Dlk-Dio3 gene cluster has been suggested to correlate with the pluripotency of iPS cells1. However, evidence from recent studies has demonstrated that loss of imprinting at the Dlk-Dio3 locus did not correlate strictly with the reduced pluripotency of iPS cells. Therefore, it becomes indispensable to exploit other reliable molecular markers for evaluating the quality of iPS cells accurately. In the present study, we successfully utilize the sequential reprogramming approach and produce all-iPS mice to six generations using iPS cell lines derived from different cell lineages which contain the same proviral integration in the genome. By comparing the global gene expression and epigenetic modifications of both “tetra-on” and corresponding “tetra-off” iPS cell lines established from either mesenchymal or hematopoietic lineages through deep sequencing analysis of mRNA expression, small RNA profiling, histone modifications (H3K4m2, H3K4me3 and H3K27me3) and DNA methylation, very few differences are detected among all the iPS cell lines investigated. However, we find that two imprinted genes, disruption of which correlate with the reduced pluripotency of iPS cells. Therefore, our data not only provide the first demonstration that producing of all-iPS mice to six generations is feasible, but reveal that two imprinted regions can be served as pluripotency markers of iPS cells Examination of the expression small RNA in 13 cell types
2013-12-06 | E-GEOD-36291 | biostudies-arrayexpress
Project description:Full pluripotency of induced pluripotent stem (iPS) cells has been determined as viable all-iPS mice can be generated through tetraploid complementation. Subsequently, activation of imprinted Dlk-Dio3 gene cluster has been suggested to correlate with the pluripotency of iPS cells1. However, evidence from recent studies has demonstrated that loss of imprinting at the Dlk-Dio3 locus did not correlate strictly with the reduced pluripotency of iPS cells. Therefore, it becomes indispensable to exploit other reliable molecular markers for evaluating the quality of iPS cells accurately. In the present study, we successfully utilize the sequential reprogramming approach and produce all-iPS mice to six generations using iPS cell lines derived from different cell lineages which contain the same proviral integration in the genome. By comparing the global gene expression and epigenetic modifications of both “tetra-on” and corresponding “tetra-off” iPS cell lines established from either mesenchymal or hematopoietic lineages through deep sequencing analysis of mRNA expression, small RNA profiling, histone modifications (H3K4m2, H3K4me3 and H3K27me3) and DNA methylation, very few differences are detected among all the iPS cell lines investigated. However, we find that two imprinted genes, disruption of which correlate with the reduced pluripotency of iPS cells. Therefore, our data not only provide the first demonstration that producing of all-iPS mice to six generations is feasible, but reveal that two imprinted regions can be served as pluripotency markers of iPS cells Examination of DNA methylation in 13 cell types
2013-12-06 | E-GEOD-36293 | biostudies-arrayexpress
Project description:Full pluripotency of induced pluripotent stem (iPS) cells has been determined as viable all-iPS mice can be generated through tetraploid complementation. Subsequently, activation of imprinted Dlk-Dio3 gene cluster has been suggested to correlate with the pluripotency of iPS cells1. However, evidence from recent studies has demonstrated that loss of imprinting at the Dlk-Dio3 locus did not correlate strictly with the reduced pluripotency of iPS cells. Therefore, it becomes indispensable to exploit other reliable molecular markers for evaluating the quality of iPS cells accurately. In the present study, we successfully utilize the sequential reprogramming approach and produce all-iPS mice to six generations using iPS cell lines derived from different cell lineages which contain the same proviral integration in the genome. By comparing the global gene expression and epigenetic modifications of both “tetra-on” and corresponding “tetra-off” iPS cell lines established from either mesenchymal or hematopoietic lineages through deep sequencing analysis of mRNA expression, small RNA profiling, histone modifications (H3K4m2, H3K4me3 and H3K27me3) and DNA methylation, very few differences are detected among all the iPS cell lines investigated. However, we find that two imprinted genes, disruption of which correlate with the reduced pluripotency of iPS cells. Therefore, our data not only provide the first demonstration that producing of all-iPS mice to six generations is feasible, but reveal that two imprinted regions can be served as pluripotency markers of iPS cells Examination of 3 different histone modifications in 13 cell types
2013-12-06 | E-GEOD-36292 | biostudies-arrayexpress
Project description:Full pluripotency of induced pluripotent stem (iPS) cells has been determined as viable all-iPS mice can be generated through tetraploid complementation. Subsequently, activation of imprinted Dlk-Dio3 gene cluster has been suggested to correlate with the pluripotency of iPS cells1. However, evidence from recent studies has demonstrated that loss of imprinting at the Dlk-Dio3 locus did not correlate strictly with the reduced pluripotency of iPS cells. Therefore, it becomes indispensable to exploit other reliable molecular markers for evaluating the quality of iPS cells accurately. In the present study, we successfully utilize the sequential reprogramming approach and produce all-iPS mice to six generations using iPS cell lines derived from different cell lineages which contain the same proviral integration in the genome. By comparing the global gene expression and epigenetic modifications of both “tetra-on” and corresponding “tetra-off” iPS cell lines established from either mesenchymal or hematopoietic lineages through deep sequencing analysis of mRNA expression, small RNA profiling, histone modifications (H3K4m2, H3K4me3 and H3K27me3) and DNA methylation, very few differences are detected among all the iPS cell lines investigated. However, we find that two imprinted genes, disruption of which correlate with the reduced pluripotency of iPS cells. Therefore, our data not only provide the first demonstration that producing of all-iPS mice to six generations is feasible, but reveal that two imprinted regions can be served as pluripotency markers of iPS cells
2013-12-06 | GSE36293 | GEO