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- 2017.1
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Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells is unknown. In the present study, we elucidated the importance of Trib2 in maintaining pluripotency in mouse ES cells and in generating iPS cells from somatic cells through the reprogramming process. Trib2 expression decreased as ES cells differentiated, and Trib2 knockdown in ES cells changed their colony morphology while reducing the activity of alkaline phosphatase and the expression of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4.
Trib2 directly interacted with Oct4 and elevated Oct4 promoter activity. During the generation of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse embryonic fibroblasts, whereas Trib2 overexpression significantly increased their reprogramming efficiency. In summary, our results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process.
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참고문헌 (26)
참고문헌 신청
[학술지(정기간
Avilion AA / 2003 / Multipotent cell lineages in early mouse development depend on SOX2function / Genes Dev 17 : 126 ~ 140
Brandenberger R / 2004 / Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation / Nat Biotechnol 22 : 707 ~ 716
Brehm A / 1997 / The carboxy-terminal transactivation domain of Oct-4 acquires cell specificity through the POU domain / Mol Cell Biol 17 : 154 ~ 162
Chen X / 2008 / Integration of external signaling pathways with the core transcriptional network in embryonic stem cells / Cell 133 : 1106 ~ 1117
Avilion AA / 2003 / Multipotent cell lineages in early mouse development depend on SOX2function / Genes Dev 17 : 126 ~ 140
Brandenberger R / 2004 / Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation / Nat Biotechnol 22 : 707 ~ 716
Brehm A / 1997 / The carboxy-terminal transactivation domain of Oct-4 acquires cell specificity through the POU domain / Mol Cell Biol 17 : 154 ~ 162
Chen X / 2008 / Integration of external signaling pathways with the core transcriptional network in embryonic stem cells / Cell 133 : 1106 ~ 1117
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