title: Gene expression of OCT4, SOX2, KLF4 and MYC (OSKM) induced pluripotent stem cells: identification for potential mechanisms.
abstract: BACKGROUND
  Somatic 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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2503890341543007 .
authors.affiliation: School of Information Science and Technology, Sun Yat-sen University, Higher Education Mega Center, No.132 East Outer Ring Road, Guangzhou, China. caiyanningmitl@sina.com.|SYSU-CMU Shunde International Joint Research Institute (JRI), Shunde, Guangdong, China. caiyanningmitl@sina.com.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Cai
authors.affiliation: School of Information Science and Technology, Sun Yat-sen University, Higher Education Mega Center, No.132 East Outer Ring Road, Guangzhou, China. issdxh@mail.sysu.edu.cn.|SYSU-CMU Shunde International Joint Research Institute (JRI), Shunde, Guangdong, China. issdxh@mail.sysu.edu.cn.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Dai
authors.affiliation: School of Information Science and Technology, Sun Yat-sen University, Higher Education Mega Center, No.132 East Outer Ring Road, Guangzhou, China. sunnydoll78@163.com.|SYSU-CMU Shunde International Joint Research Institute (JRI), Shunde, Guangdong, China. sunnydoll78@163.com.
authors.forename: Qianhua
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Information Science and Technology, Sun Yat-sen University, Higher Education Mega Center, No.132 East Outer Ring Road, Guangzhou, China. daizhim@mail.sysu.edu.cn.|SYSU-CMU Shunde International Joint Research Institute (JRI), Shunde, Guangdong, China. daizhim@mail.sysu.edu.cn.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Dai
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors