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Gene expression of OCT4, SOX2, KLF4 and MYC (OSKM) induced pluripotent stem cells: identification for potential mechanisms.

Cai Y, Dai X, Zhang Q, Dai Z - Diagn Pathol (2015)

Bottom Line: Down-regulated DEGs at 72 h were significantly enriched in focal adhesion pathway which was similar to iPS cells.Furthermore, the targets of six selected TFs were mainly enriched in screened DEGs.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.

View Article: PubMed Central - PubMed

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.

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.

Conclusion: 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.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2503890341543007 .

No MeSH data available.


Related in: MedlinePlus

Regulatory networks for differentially expressed genes in iPS and ES cells. Yellow circle represents transcription factor. Red circle represents up-regulated differentially expressed gene (DEG) and green circle represents down-regulated DEG.
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Fig4: Regulatory networks for differentially expressed genes in iPS and ES cells. Yellow circle represents transcription factor. Red circle represents up-regulated differentially expressed gene (DEG) and green circle represents down-regulated DEG.

Mentions: To gain insight into the enriched targets for TFs, regulatory networks were constructed for TFs and DEGs (Figures 3 and 4). In different regulatory network, the number of target DEGs varied widely (Table 5). In OSKM-induced HFF1 cells, screened DEGs were significantly targeted by STAT5B, FOXF2 and GATA2, but in iPS and ES cells, screened DEGs were mainly targeted by STAT5B, FOXA3 and FOXF2. As a result, GATA2 and FOXA3 might be the difference between somatic cells and pluripotent cells.Figure 3


Gene expression of OCT4, SOX2, KLF4 and MYC (OSKM) induced pluripotent stem cells: identification for potential mechanisms.

Cai Y, Dai X, Zhang Q, Dai Z - Diagn Pathol (2015)

Regulatory networks for differentially expressed genes in iPS and ES cells. Yellow circle represents transcription factor. Red circle represents up-regulated differentially expressed gene (DEG) and green circle represents down-regulated DEG.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4414430&req=5

Fig4: Regulatory networks for differentially expressed genes in iPS and ES cells. Yellow circle represents transcription factor. Red circle represents up-regulated differentially expressed gene (DEG) and green circle represents down-regulated DEG.
Mentions: To gain insight into the enriched targets for TFs, regulatory networks were constructed for TFs and DEGs (Figures 3 and 4). In different regulatory network, the number of target DEGs varied widely (Table 5). In OSKM-induced HFF1 cells, screened DEGs were significantly targeted by STAT5B, FOXF2 and GATA2, but in iPS and ES cells, screened DEGs were mainly targeted by STAT5B, FOXA3 and FOXF2. As a result, GATA2 and FOXA3 might be the difference between somatic cells and pluripotent cells.Figure 3

Bottom Line: Down-regulated DEGs at 72 h were significantly enriched in focal adhesion pathway which was similar to iPS cells.Furthermore, the targets of six selected TFs were mainly enriched in screened DEGs.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.

View Article: PubMed Central - PubMed

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.

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.

Conclusion: 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.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2503890341543007 .

No MeSH data available.


Related in: MedlinePlus