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Genome-wide screening in human kidney organoids identifies novel aspects of nephrogenesis

Ungricht, Rosemarie, Guibbal, Laure, Lasbennes-Eckerlen, Marie-Christine, Orsini, Vanessa, Beibel, Martin, Waldt, Annick, Cuttat-Theurillat, Rachel, Carbone, Walter, Basler, Anne, Roma, Guglielmo, Nigsch, Florian, Tchorz, Jan, Hoepfner, Dominic and Hoppe, Philipp (2022) Genome-wide screening in human kidney organoids identifies novel aspects of nephrogenesis. Cell stem cell, 29 (1). p. 160. ISSN 19345909


Human organoids allow studying proliferation, lineage specification, and three-dimensional tissue development. Here, we present the first genome-wide CRISPR screen in iPSC-derived kidney organoids. The combination of inducible genome editing, longitudinal sampling and endpoint sorting of tubular and stromal cells generated a complex, high quality dataset uncovering a broad spectrum of novel biology from early development to ‘adult’ epithelial morphogenesis. Our functional dataset allows improving mesoderm induction by ROCK inhibition, contains monogenetic and complex trait kidney disease genes, confirms two novel CAKUT genes (CCDC170 and MYH7B), and provides a large candidate list of ciliopathy-related genes. Finally, the identification of a cis-inhibitory effect of Jagged1 controlling epithelial proliferation shows how mosaic knockouts in pooled CRISPR screening can discover novel ways of communication between heterogeneous cell populations in complex tissues. Collectively, these data serve both as a rich resource for the kidney community and as a benchmark for future iPSC-derived organoid CRISPR screens.

Item Type: Article
Date Deposited: 03 Mar 2022 00:45
Last Modified: 03 Mar 2022 00:45


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