| Literature DB >> 30573816 |
Belinda Phipson1, Pei X Er1, Alexander N Combes1,2, Thomas A Forbes1,3,4, Sara E Howden1,2, Luke Zappia1,5, Hsan-Jan Yen1, Kynan T Lawlor1, Lorna J Hale1,4, Jane Sun6, Ernst Wolvetang6, Minoru Takasato1,7, Alicia Oshlack1,5, Melissa H Little8,9,10.
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.Entities:
Mesh：
Year: 2018 PMID： 30573816 PMCID： PMC6634992 DOI： 10.1038/s41592-018-0253-2
Source DB: PubMed Journal: Nat Methods ISSN： 1548-7091 Impact factor: 28.547