Creating innovative bio-convergent technologies for better human life

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제목 : Self-renewal and signaling pathways in human
embryonic stem cells

연사 : Yong-Mahn Han, Ph.D.

소속: Laboratory of Development and Differentiation,
Korea Research Institute of Bioscience and Biotechnology
(KRIBB)

일시: 2005. 11. 29 (Tue) 16:30-17:40

장소: Room 219, Chung Moon Soul Building (E16)


Embryonic stem cells (ESC) derived from early embryos are able to maintain indefinitely under the optimal culture conditions by self-renewing and differentiate into all cell types of embryo proper. Although a variety of signaling pathways are involved in self-renewal of stem cells, little information is available regarding the molecular networks of the signaling pathways in human ESC. In this study, expression profiles of key genes related to the developmentally important signaling pathways such as BMP4, TGF-b, FGF4, Wnt, Hh, Notch, and JAK/STAT signaling, were examined to understand self-renewal of human ESC in the molecular level. In BMP4, TGF-b FGF4 and signaling pathways, extracellular molecules, ligands and antagonists, were highly expressed in human ESC as compared to the human embryoid body (EB). In Wnt, Hh and Notch signaling, expression of intracellular molecules was enriched in human ESC. In JAK-STAT signaling pathway, no difference was detected in the expression levels of the genes between human ESC and EB. These results suggest that self-renewal of human ESC is likely to be maintained by the coordinated regulations of signaling specific molecules. Another experiment was conducted to investigate the expression profiles of cell cycle-related genes in hESCs. Key factors such as cyclins and cyclin-dependent kinases (Cdks), which are responsible for G1/S phase progression, were highly expressed in hESCs. Cell cycle inhibitory factors such as CKI family and p53-related cell cycle arresting factors showed low expression level in hESCs. Interestingly, transcripts of p53-dependent cell cycle arresting factors were low although p53 was highly transcribed in hESCs. Mdm2, negative regulator of p53, was also highly expressed in hESCs, which may be responsible for low expression of the p53-related cell cycle arrest factors. Our results indicate that a paucity of most cell cycle arresting factors could not inhibit abundant cell cycle progression factors, eventually shortening of the G1-phase in hESCs. Our findings are helpful for understanding the molecular mechanisms of self-renewal and differentiation in human embryonic stem cells.