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Generation of kidney ureteric bud and collecting duct organoids that recapitulate kidney branching morphogenesis

Zipeng Zeng, Biao Huang, Riana K. Parvez, Yidan Li, Jyunhao Chen, Ariel Vonk, Matthew E. Thornton, Tadrushi Patel, Elisabeth A. Rutledge, Albert D. Kim, Jingying Yu, Nuria Pastor-Soler, Kenneth R. Hallows, Brendan H. Grubbs, Jill A. McMahon, Andrew P. McMahon, Zhongwei Li
doi: https://doi.org/10.1101/2020.04.27.049031
Zipeng Zeng
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Biao Huang
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Riana K. Parvez
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Yidan Li
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Jyunhao Chen
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Ariel Vonk
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Matthew E. Thornton
3Division of Maternal Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Tadrushi Patel
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Elisabeth A. Rutledge
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Albert D. Kim
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Jingying Yu
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Nuria Pastor-Soler
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Kenneth R. Hallows
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Brendan H. Grubbs
3Division of Maternal Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Jill A. McMahon
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Andrew P. McMahon
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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Zhongwei Li
1USC/UKRO Kidney Research Center, Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
2Deptartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
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  • For correspondence: zhongwei.li@med.usc.edu
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Abstract

Kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney’s collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from pluripotent human stem cells. UB organoids differentiate into CD organoids in vitro, with differentiated cell types adopting spatial assemblies reflective of the adult kidney collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Combining efficient gene editing with the UB organoid model will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting system.

One sentence summary Collecting duct organoids derived from primary mouse and human ureteric bud progenitor cells and human pluripotent stem cells provide an in vitro platform for genetic dissection of development, regeneration and diseases of the mammalian collecting system.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 28, 2020.
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Generation of kidney ureteric bud and collecting duct organoids that recapitulate kidney branching morphogenesis
Zipeng Zeng, Biao Huang, Riana K. Parvez, Yidan Li, Jyunhao Chen, Ariel Vonk, Matthew E. Thornton, Tadrushi Patel, Elisabeth A. Rutledge, Albert D. Kim, Jingying Yu, Nuria Pastor-Soler, Kenneth R. Hallows, Brendan H. Grubbs, Jill A. McMahon, Andrew P. McMahon, Zhongwei Li
bioRxiv 2020.04.27.049031; doi: https://doi.org/10.1101/2020.04.27.049031
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Generation of kidney ureteric bud and collecting duct organoids that recapitulate kidney branching morphogenesis
Zipeng Zeng, Biao Huang, Riana K. Parvez, Yidan Li, Jyunhao Chen, Ariel Vonk, Matthew E. Thornton, Tadrushi Patel, Elisabeth A. Rutledge, Albert D. Kim, Jingying Yu, Nuria Pastor-Soler, Kenneth R. Hallows, Brendan H. Grubbs, Jill A. McMahon, Andrew P. McMahon, Zhongwei Li
bioRxiv 2020.04.27.049031; doi: https://doi.org/10.1101/2020.04.27.049031

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