Evaluation of variability in human kidney organoids

Belinda Phipson, Pei X. Er, Alexander N. Combes, Thomas A. Forbes, Sara E. Howden, Luke Zappia, Hsan Jan Yen, Kynan T. Lawlor, Lorna J. Hale, Jane Sun, Ernst Wolvetang, Minoru Takasato, Alicia Oshlack, Melissa H. Little

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalNature Methods
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

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