Abstract:
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
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