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
|Author:||Tan, Zenglai1; Ottavainen, Vuokko1; Rak-Raszewska, Aleksandra1;|
1Biocenter Oulu, Infotech Oulu, Center for Cell Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu
|Online Access:||PDF Full Text (PDF, 2.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe201901021134
|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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
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
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.