University of Oulu

Tan, Z., Shan, J., Rak-Raszewska, A., Vainio, S. (2018) Embryonic Stem Cells Derived Kidney Organoids as Faithful Models to Target Programmed Nephrogenesis. Scientific Reports, 8 (1), 16618. doi:10.1038/s41598-018-34995-3

Embryonic stem cells derived kidney organoids as faithful models to target programmed nephrogenesis

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Author: Tan, Zenglai1; Ottavainen, Vuokko1; Rak-Raszewska, Aleksandra1;
Organizations: 1Biocenter Oulu, Infotech Oulu, Center for Cell Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
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Language: English
Published: Springer Nature, 2018
Publish Date: 2019-01-02


The kidney is a complex organ that is comprised of thousands of nephrons developing through reciprocal inductive interactions between metanephric mesenchyme (MM) and ureteric 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−/− mutants fail to form pretubular aggregates (PTA) and therefore lack functional nephrons. Here, we generated mouse embryonic stem cell (mESC) line lacking 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 nephrogenesis by 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.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 8
Article number: 16618
DOI: 10.1038/s41598-018-34995-3
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by H2020 Marie Skłodowska-Curie Actions Innovative Training Network “RENALTRACT”, (Project ID 642937), Centre of Excellence grant (2012-2017 251314), the European Community’s Seventh Framework Programme (FP7/2007-2013; grant FP7-HEALTH-F5-2012-INNOVATION-1 EURenOmics 305608) and Finnish Cultural Foundation (personal grant to A.R.R).
EU Grant Number: (642937) RENALTRACT - Development and disease of the renal tract
(305608) EURENOMICS - European Consortium for High-Throughput Research in Rare Kidney Diseases
Academy of Finland Grant Number: 251314
Detailed Information: 251314 (Academy of Finland Funding decision)
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