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Reprogramming of human somatic cells to pluripotency with defined factors

ABSTRACT: Pluripotency, the capacity of embryo-derived stem cells to generate all tissues in the organism, can be induced in somatic cells by nuclear transfer into oocyte, fusion with embryonic stem cells, and for male germ cells by cell culture alone. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4, and Myc) to yield induced Pluripotent Stem (iPS) cells. Using the same four factors, we have derived iPS cells from human embryonic stem cell-derived fibroblasts, primary human fetal cells, and diverse cells of neonatal and adult human origin. The human iPS cells manifest the colony morphology, gene expression patterns, and epigenetic characteristics of human Embryonic Stem (hES) cells, and form well-differentiated teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogram human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture. Biological replicates: GSM248201 and GSM248202; GSM248205 and GSM248206; GSM248207 and GSM248208; GSM248209 and GSM248210; GSM248211 and GSM248212; GSM248213 and GSM248214. Sample descriptions: H1-OGN: ES cells expressing GFP-NEO marker under OCT4 promoter dH1f: differentiated H1-OGN fibroblasts dHcf16: differentiated H1-OGN cloned fibroblasts MRC5: fetal lung fibroblasts BJ1: neonatal fibroblasts Keywords: cellular reprogramming

ORGANISM(S): Homo sapiens

PROVIDER: GSE9832 | GEO | 2007/12/10

SECONDARY ACCESSION(S): PRJNA103803

REPOSITORIES: GEO

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Project description:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation. This model is described in the article: In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach. Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R BMC Genomics, 2009, 10:314 Abstract: BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency. RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation. CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies. This model is hosted on BioModels Database and identified by: MODEL1305010000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Reprogramming of human somatic cells to pluripotency with defined factors

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