Lunch with Bon-Kyoung Koo at Campea Thursday at 12:00
Abstract:
The identification of LGR5+ intestinal stem cells helped us to understand various aspects of adult stem cells and led us to establish primary 3D organotypic stem cell culture system. Expression profiling of LGR5+ intestinal stem cells identified a number of stem cell-specific genes, such as RNF43. Functional genetic studies of RNF43 and its paralogue ZNRF3 showed that they are important negative feedback regulators of the Wnt signalling pathway. Intestinal epithelium-specific deletion of RNF43 and ZNRF3 induced rapid formation of tumours which consisted mainly of intestinal stem cells, suggesting they negatively regulate uncontrolled outgrowth of adult stem cells. In addition, the primary 3D organoid culture technique was combined with CRISPR/Cas genome engineering tools to grow patient adult stem cells and to perform precise gene correction of cystic fibrosis patient mutations. This offers a promising alternative for the supply of self-originated tissues without the use of iPSC reprograming and differentiation.
References
Koo BK*, Stange DE* et al. Controlled gene expression in primary Lgr5 organoid cultures [Nature Methods] 2011 Dec 4;9(1):81-3.
Koo BKet al. Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. [Nature] 2012 Aug 30;488(7413):665-9.
Stange DE*, Koo BK* et al. Differentiated Troy+ chief cells act as 'reserve' stem cells to generate all lineages of the stomach epithelium [Cell] 2013 Oct 10;155(2): 357–368.
Schwank G*, Koo BK* et al. Functional repair of the CFTR locus in primary intestinal stem cells of cystic fibrosis patients [Cell Stem Cell] 2013 Dec 5;13(6):653-8.
Koo BK*†, van Es JH* et al. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant tumors [PNAS] 2015 May 28. pii: 2015081113.
