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인간 배아줄기세포-특이적 인자의 리간드를 이용한 세포 줄기성 조절
- Alternative Title
- The regulation of stemness using the ligands of human ES cell-specific factor
- Author(s)
- 김지인
- Alternative Author(s)
- Jiin Kim
- Advisor
- 이명애
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2017-08
- Language
- eng
- Keyword
- Embryonic stem cell; Stemness; Cell proliferation; GPCR
- Alternative Abstract
- Human embryonic stem cells (hESC) have been regarded as promising resources for therapeutic uses with self-renewal property. Recent studies have discovered various transcription factors underlying stemness of hESCs. However, no membrane receptors related to stemness are known so far. We identified a novel GPCR protein HECAT5 as a candidate molecule regulating stemness using digital differential display (DDD). When we overexpressed HECAT5 in hNSC and HEK293 cells, it dramatically increased cell proliferation as well as S phase population. While investigating signaling pathway underlying the effect of HECAT5 in cell proliferation, we found that treatment of Gq protein inhibitor, YM254890, did not affect cell proliferation induced by HECAT5. Furthermore, the level of ERK and AKT which are downstream molecules of β-arrestin pathway did not change in HECAT5-overexpressed cells. Next, we aimed to identify ligands which may modulate HECAT5 activity. We found nonanoic acid which showed approximately 70% binding affinity to HECAT5 via ODORactor website. We observed that nonanoic acid increased cell proliferation, while there was no difference in ERK and AKT level, which means it is not HECAT5-specific ligand. Generally, GPCR goes through conformational change upon their activation and Toggle switch and Ionic lock are involved in this mechanism. Based on the fact that HECAT5 has both Toggle switch and ionic lock with highly conserved and candidate odors analyzed from reference dataset, we established the homology model of HECAT5. This results in approximately 140 candidate chemicals after screening various commercial chemical libraries. In this respect, we anticipate that HECAT5 activity modulators may play a role in increasing the efficiency of iPSC generation or in blocking certain type of cancer cells.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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