Unknown,Transcriptomics,Genomics,Proteomics

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Generation of human induced pluripotent stem cells from mesenchymal cells of gut mesentery by Oct4/Sox2/Nanog

ABSTRACT: Background and aim: Human Induced pluripotent stem (iPS) cells have been derived from dermal ﬁbroblasts, keratinocytes and blood cells by ectopic expression of defined transcription factors.1–5 Application of this approach in human cells would have enormous potential and generate patient-specific pluripotent stem cells to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. In the present study, we investigated whether genetically marked human mesenchymal cells of gut mesentery may give rise to iPS cells. Methods: We used lentiviruses to express Oct4, Sox2, Nanog in mesenchymal cells of gut mesentery, then generated iPS cells were identified in many aspects including morphology, pluripotent markers, global gene expression profile, DNA methylation status at pluripotent cell-speciﬁc genes, embryoid bodies and terotomas formation. Results: The resulting iPS cells from mesenchymal cells of gut mesentery were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, and epigenetic status of pluripotent cell-speciﬁc genes. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. DNA ﬁngerprinting showed that the human iPS cells were derived from the donor cells and are not a result of contamination. one sample/variable

ORGANISM(S): Homo sapiens

SUBMITTER: Yang Li

PROVIDER: E-GEOD-18180 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Generation of human-induced pluripotent stem cells from gut mesentery-derived cells by ectopic expression of OCT4/SOX2/NANOG.

Li Yang Y Zhao Hongxi H Lan Feng F Lee Andrew A Chen Liu L Lin Changsheng C Yao Yuanqing Y Li Lingsong L

Cellular reprogramming 20100601 3

Induced pluripotent stem (iPS) cells have been generated from human somatic cells by ectopic expression of defined transcription factors. Application of this approach in human cells may have enormous potential to generate patient-specific pluripotent stem cells. However, traditional methods of reprogramming in human somatic cells involve the use of oncogenes c-MYC and KLF4, which are not applicable to clinical translation. In the present study, we investigated whether human fetal gut mesentery-d ...[more]

PMID: 20698766

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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.

Dataset Information

Generation of human induced pluripotent stem cells from mesenchymal cells of gut mesentery by Oct4/Sox2/Nanog

Publications

Generation of human-induced pluripotent stem cells from gut mesentery-derived cells by ectopic expression of OCT4/SOX2/NANOG.

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