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Modeling Kidney Development, Disease, and Plasticity with Clonal Expandable Nephron Progenitor Cells and Nephron Organoids by Biao Huang; Zipeng Zeng; Hui Li; Zexu Li; Xi Chen; Jinjin Guo; Chennan C. Zhang; Megan E. Schreiber; Ariel C. Vonk; Tianyuan Xiang; Tadrushi Patel; Yidan Li; Riana K. Parvez; Balint Der; Jyun Hao Chen; Zhenqing Liu; Matthew E. Thornton; Brendan H. Grubbs; Yarui Diao; Yali Dou; Ksenia Gnedeva; Nils O. Lindström; Qilong Ying; Nuria M. Pastor-Soler; Teng Fei; Kenneth R. Hallows; Andrew P. McMahon; Zhongwei Li is a scholarly article available to read on EtoBox.

What is Modeling Kidney Development, Disease, and Plasticity with Clonal Expandable Nephron Progenitor Cells and Nephron Organoids about?

## SUMMARY: Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The synthetic niche reprograms differentiated nephron cells into NPC state, recapitulating the plasticity of developing nephron __in vivo__. Scalability and ease of genome-editing in the cultured NPCs allow for genome-wide CRISPR screening, identifying novel genes associated with kidney development and disease. A rapid, efficient, and scalable organoid model for polycystic kidney disease was derived directly from genome-edited NPCs, and validated in drug screen. These technological platforms have broad applications to kidney development, disease, plasticity, and regeneration.

Author

Biao Huang; Zipeng Zeng; Hui Li; Zexu Li; Xi Chen; Jinjin Guo; Chennan C. Zhang; Megan E. Schreiber; Ariel C. Vonk; Tianyuan Xiang; Tadrushi Patel; Yidan Li; Riana K. Parvez; Balint Der; Jyun Hao Chen; Zhenqing Liu; Matthew E. Thornton; Brendan H. Grubbs; Yarui Diao; Yali Dou; Ksenia Gnedeva; Nils O. Lindström; Qilong Ying; Nuria M. Pastor-Soler; Teng Fei; Kenneth R. Hallows; Andrew P. McMahon; Zhongwei Li

Publisher

Cold Spring Harbor Laboratory

Published

2023

Language

EN