Evaluation of variability in human kidney organoids

kidney
organoids
variability
rna-seq
single-cell
Authors

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

Date

December 1, 2018

Links
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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.

Citation

BibTeX citation:
@article{phipson2018,
  author = {Phipson, Belinda and X Er, Pei and N Combes, Alexander and A
    Forbes, Thomas and E Howden, Sara and Zappia, Luke and Yen, Hsan-Jan
    and T Lawlor, Kynan and J Hale, Lorna and Sun, Jane and Wolvetang,
    Ernst and Takasato, Minoru and Oshlack, Alicia and H Little,
    Melissa},
  title = {Evaluation of Variability in Human Kidney Organoids},
  journal = {Nature methods},
  volume = {16},
  number = {1},
  pages = {79-87},
  date = {2018-12-01},
  url = {https://lazappi.id.au/publications/2018-phipson-variability/},
  doi = {10.1038/s41592-018-0253-2},
  issn = {1548-7091, 1548-7105},
  langid = {en},
  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.}
}
For attribution, please cite this work as:
Phipson, Belinda, Pei X Er, Alexander N Combes, Thomas A Forbes, Sara E Howden, Luke Zappia, Hsan-Jan Yen, et al. 2018. “Evaluation of Variability in Human Kidney Organoids.” Nature Methods 16 (1): 79–87. https://doi.org/10.1038/s41592-018-0253-2.