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Nat Methods. 2019 Jan;16(1):79-87. doi: 10.1038/s41592-018-0253-2. Epub 2018 Dec 20.

Evaluation of variability in human kidney organoids.

Author information

1
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
2
Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
3
Department of Nephrology, Royal Children's Hospital, Melbourne, Victoria, Australia.
4
Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
5
School of Biosciences, The University of Melbourne, Melbourne, Victoria, Australia.
6
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
7
RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
8
Murdoch Children's Research Institute, Melbourne, Victoria, Australia. melissa.little@mcri.edu.au.
9
Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia. melissa.little@mcri.edu.au.
10
Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia. melissa.little@mcri.edu.au.

Abstract

The utility of human pluripotent stem cell-derived kidney organoids relies implicitly on the robustness and transferability of the protocol. Here we analyze the sources of transcriptional variation in a specific kidney organoid protocol. Although individual organoids within a differentiation batch showed strong transcriptional correlation, we noted significant variation between experimental batches, particularly in genes associated with temporal maturation. Single-cell profiling revealed shifts in nephron patterning and proportions of component cells. Distinct induced pluripotent stem cell clones showed congruent transcriptional programs, with interexperimental and interclonal variation also strongly associated with nephron patterning. Epithelial cells isolated from organoids aligned with total organoids at the same day of differentiation, again implicating relative maturation as a confounder. This understanding of experimental variation facilitated an optimized analysis of organoid-based disease modeling, thereby increasing the utility of kidney organoids for personalized medicine and functional genomics.

PMID:
30573816
DOI:
10.1038/s41592-018-0253-2

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