Outline of the study (IMAGE)

Kanazawa University

Outline of the study

Caption

A. Outline of GeCKO screening using organoids. Gastric organoids are established from mice that allow visualization of tissue stem cells; genes are randomly rendered loss-of-function by introducing a mouse CRISPR gRNA library for gene knockout. Thereafter, organoids that proliferate in a Wnt signaling-independent manner are collected and responsible genes are identified by using a next generation sequencer.</br> B. The important point revealed in this study. The genes <i>Alk</i>, <i>Bclaf3</i> and <i>Prkra</i> are expressed in differentiated cells of gastric glands. <i>Alk</i> destabilizes Gsk3&beta; by phosphorylation, thus suppressing Wnt signaling. On the other hand, <i>Bclaf3</i> and <i>Prkra</i> negatively regulate <i>Reg</i> gene expressions that are essential for proliferation of gastric epithelial cells through suppressing the expression of interleukins 11 (IL-11) and 23 (IL-23). It is thought that the stemness of gastric tissue stem cells is determined by cooperation of <i>Alk</i>, <i>Bclaf3</i> and <i>Prkra</i>.

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Kanazawa University

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