| 생명시스템연구원/ 단백질기능제어이행연구센터(TRCP/ERC) 특별 세미나 |
연자: Professor Hans Clevers
일시 : 2013년 10월 11일(금) 5:00～6:00 PM
장소 : 연세대학교 장기원국제회의실(연세·삼성 학술정보관 7층)
주관 : 단백질기능제어이행연구센터(TRCP/ERC), 생명시스템연구원
후원 : 연세대학교 생명시스템대학, 글로벌 통합바이오 사업단
“Hans Clevers” 교수는 최근 “Breakthrough Prize in Life Science” 수상을 포함한 수많은 수상을 하였으며, “줄기세포”와 “암” 관련 분야의 새로운 전기를 마련한 세계적인 석학 입니다.
관심 있는 분들의 많은 참석을 바랍니다. (*최근 3년 업적 파일 첨부)
Hans Clevers, M.D., Ph.D.
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences & University Medical Center Utrecht, Netherlands
Hans Clevers obtained his MD degree in 1984 and his PhD degree in 1985 from the University Utrecht, the Netherlands. His postdoctoral work (1986-1989) was done with Cox Terhorst at the Dana-Farber Cancer Institute of the Harvard University, Boston, USA.
From 1991-2002 Hans Clevers was Professor in Immunology at the University Utrecht and, since 2002, Professor in Molecular Genetics. From 2002-2012 he was director of the Hubrecht Institute in Utrecht . Since 2012 he is President of the Royal Netherlands Academy of Arts and Sciences (KNAW).
The intestinal epithelium is the most rapidly self-renewing mammalian tissue. Lgr5 is a gene transcribed in cycling, crypt base columnar cells at the crypt base. Using lineage tracing experiments the Lgr5+ve cells were identified as the stem cells of the intestinal epithelium. Furthermore, Lgr5+ve stem cells can initiate ever-expanding organoids in vitro. The Lgr5+ve stem cell hierarchy of differentiation is maintained in these organoids. Thus, intestinal crypt-villus units can be built from a single stem cell in the absence of a non-epithelial cellular niche.
Although, Lgr5 stem cells persist life-long, crypts drift toward clonality quickly. The cellular dynamics are consistent with a model in which the stem cells divide symmetrically, and stochastically adopt stem or transient amplifying cell fates after cell division.
Lgr5 stem cells are interspersed between differentiated Paneth cells, which produce all essential signals for stem-cell maintenance. Co-culturing of sorted stem cells with Paneth cells dramatically improves organoid formation. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells.
Intestinal cancer is initiated by Wnt pathway-activating mutations in genes such as APC. Deletion of APC in stem cells, but not in other crypt cells results in neoplasia, identifying the stem cell as the cell-of-origin of adenomas. Moreover, a stem cell/progenitor cell hierarchy is maintained in stem cell-derived adenomas, lending support to the “cancer stem cell”-concept.