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pmid:25907774
Gene expression of OCT4, SOX2, KLF4 and MYC (OSKM) induced pluripotent stem cells: identification for potential mechanisms.
Yanning Cai · Xianhua Dai · Qianhua Zhang · Zhiming Dai
Diagnostic pathology · 2015 doi:10.1186/s13000-015-0263-7
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Complete file
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We aimed to gain insights into the early mechanisms underlying the induction of pluripotency.\nMETHODS: GSE28688 containing 14 gene expression profiles were downloaded from GEO, including untreated human neonatal foreskin fibroblasts (HFF1) as control, OSKM-induced HFF1 (at 24, 48, 72 h post-transduction of OSKM encoding viruses), two iPS cell lines, and two embryonic stem (ES) cell lines. Differentially expressed genes (DEGs) were screened between different cell lines and the control by Limma package in Bioconductor. KEGG pathway enrichment analysis was performed by DAVID. The STRING database was used to construct protein-protein interaction (PPI) network. Activities and regulatory networks of transcription factors (TFs) were calculated and constructed by Fast Network Component Analysis (FastNCA).\nRESULTS: Compared with untreated HFF1, 117, 347, 557, 2263 and 2307 DEGs were obtained from three point post-transduction HFF1, iPS and ES cells. Meanwhile, up-regulated DEGs in first two days of HFF1 were mainly enriched in RIG-I-like receptor (RLR) and Toll-like receptor (TLR) signaling pathways. Down-regulated DEGs at 72 h were significantly enriched in focal adhesion pathway which was similar to iPS cells. Moreover, ISG15, IRF7, STAT1 and DDX58 were with higher degree in PPI networks during time series. Furthermore, the targets of six selected TFs were mainly enriched in screened DEGs.\nCONCLUSION: In this study, screened DEGs including ISG15, IRF7 and CCL5 participated in OSKM-induced pluripotency might attenuate immune response post-transduction through RLR and TLR signaling pathways.\nVIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2503890341543007 .", "claims": [{"id": "claim-method", "statement": "DEGs were identified from different comparisons between OSKM-induced HFF1 cells and the control, between iPS cells and the control, between ES cells and the control using Limma package [17] in Bioconductor with a t-test under Benjamini Hochberg correction [18].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25907774", "locator": "sections[4] \"Data preprocessing and DEGs screening\" paragraph 2", "quote": "DEGs were identified from different comparisons between OSKM-induced HFF1 cells and the control, between iPS cells and the control, between ES cells and the control using Limma package [17] in Bioconductor with a t-test under Benjamini Hochberg correction [18]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data under the accession number GSE28688 is available at the NCBI Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/)", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:25907774", "locator": "sections[3] \"Microarray data\" paragraph 2", "quote": "The microarray data under the accession number GSE28688 is available at the NCBI Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/)"}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study analyzed the GSE28688 microarray dataset downloaded from GEO and used the Limma package in Bioconductor to identify differentially expressed genes, identifying 117, 347, 557, 2263 and 2307 DEGs in the 24 h, 48 h, 72 h, iPS and ES comparisons, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25907774", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "GSE28688 containing 14 gene expression profiles were downloaded from GEO, including untreated human neonatal foreskin fibroblasts (HFF1) as control, OSKM-induced HFF1 (at 24, 48, 72 h post-transduction of OSKM encoding viruses), two iPS cell lines, and two embryonic stem (ES) cell lines."}, {"asset": "source:pmid:25907774", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were screened between different cell lines and the control by Limma package in Bioconductor."}, {"asset": "source:pmid:25907774", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Compared with untreated HFF1, 117, 347, 557, 2263 and 2307 DEGs were obtained from three point post-transduction HFF1, iPS and ES cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study analyzed the GSE28688 microarray dataset downloaded from GEO and used the Limma package in Bioconductor to identify differentially expressed genes, identifying 117, 347, 557, 2263 and 2307 DEGs in the 24 h, 48 h, 72 h, iPS and ES comparisons, respectively.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25907774"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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