“Embryonic Stem Cells Derived Kidney Organoids as Faithful Models to Target Programmed Nephrogenesis” is the title of a new publication by the team of Seppo Vainio (RENALTRACT Principal Investigator) and Zenglai Tan (ESR 1) at the University of Oulu. “We present protocol of generation of kidney organoid from mouse embryonic stemcell. The organoid can be used to model kidney development when combinewith genome editing technology CRISPR/Cas9. This system may provide auseful setting that will benefit personalized medicine and gene therapy”, explained the team in Oulu. Here are the abstract and the link to the article:
The kidney is a complex organ that is comprised of thousands of nephrons developing throughreciprocal inductive interactions between metanephric mesenchyme (MM) andureteric bud (UB). The MM undergoes mesenchymal to epithelial transition (MET) in response to the signaling from the UB. The secreted protein Wnt4, one of the Wnt family members, is critical for nephrogenesis as mouse Wnt4−/−mutantsfail to form pretubular aggregates (PTA) and therefore lack functionalnephrons. Here, we generated mouse embryonic stem cell (mESC) linelacking Wnt4 by applying the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9). We describe here, differentiation of the wild type and Wnt4 knockout mESCs into kidney progenitors, and such cells induced to undergo nephrogenesisby the mouse E11.5 UB mediated induction. The wild type three-dimensional (3D) self-organized organoids depict appropriately segmented nephron structures, while the Wnt4-deficient organoids fail to undergo the MET, as is the case in the phenotype of the Wnt4 knockout mouse model in vivo. In summary, we have established a platform that combine CRISPR/Cas9 and kidney organoid technologies to model kidney development in vitro and confirmed that mutant organoids are able to present similar actions as in the in vivo studies.
7th December 2018