Abstract
BackgroundSomatic cells could be reprogrammed to induced pluripotent stem cells (iPS) by ectopic expression of OCT4, SOX2, KLF4 and MYC (OSKM). We aimed to gain insights into the early mechanisms underlying the induction of pluripotency.MethodsGSE28688 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).ResultsCompared 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.ConclusionIn 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.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2503890341543007.
Highlights
Somatic cells could be reprogrammed to induced pluripotent stem cells by ectopic expression of octamer binding transcription factor 4 (OCT4), SOX2, Kruppel like factor 4 (KLF4) and myelocytomatosis viral oncogene (MYC) (OSKM)
Somatic cells can be forcibly reprogrammed to pluripotency by cell fusion, somatic cell nuclear transfer and ectopic expression of defined factors including octamer binding transcription factor 4 (OCT4), SRY related high mobility group box protein 2 (SOX2), Kruppel like factor 4 (KLF4) and myelocytomatosis viral oncogene (MYC) [4,5,6]
Differentially expressed genes (DEGs) screening In order to gain insight into the molecular events during the early stage of reprogramming, we screened DEGs from comparisons between HFF1 cells at 24, 48, 72 h post-transduction of OSKM encoding viruses and HFF1 control, between HFF1-derived induced pluripotent stem cells (iPS) cell lines and control, between the embryonic stem (ES) cell lines and control
Summary
Somatic cells could be reprogrammed to induced pluripotent stem cells (iPS) by ectopic expression of OCT4, SOX2, KLF4 and MYC (OSKM). Human embryonic stem (ES) cells have potential in cell replacement therapies using their regenerative properties. Induced pluripotent stem (iPS) cells take advantages over ES cells. It is important to highlight the need to investigate differences between iPS and ES cells. In adult tissues and organs, fully differentiated cells rarely change from one type to another. Somatic cells can be forcibly reprogrammed to pluripotency by cell fusion, somatic cell nuclear transfer and ectopic expression of defined factors including octamer binding transcription factor 4 (OCT4), SRY related high mobility group box protein 2 (SOX2), Kruppel like factor 4 (KLF4) and myelocytomatosis viral oncogene (MYC) (known as OSKM factors) [4,5,6].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
