Last updated: 2019-01-25

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Single cell analysis reveals congruence between kidney organoids and human fetal kidney

Publication: DOI Website and code: DOI

This site contains the results of the analysis presented in “Single-cell analysis reveals congruence between kidney organoids and human fetal kidney” published in Genome Medicine. Follow the links below to see the different parts of the analysis. If you want to reproduce the analysis please have a look at the Getting started page.

Abstract

Background:

Human kidney organoids hold promise for studying development, disease modelling and drug screening. However, the utility of stem cell-derived kidney tissues will depend on how faithfully these replicate normal fetal development at the level of cellular identity and complexity.

Results:

Here we present an integrated analysis of single cell datasets from human kidney organoids and human fetal kidney to assess similarities and differences between the component cell types. When overlaid, individual cell clusters contained cells from both organoid and fetal kidney with transcriptional congruence for key stromal, endothelial and nephron cell-type specific markers. Organoid enriched neural, glial and muscle progenitor populations are also evident. Major transcriptional differences between organoid and human tissue were likely related to technical artefacts. Cell type-specific comparisons revealed differences in stromal, endothelial, and nephron progenitor cell types including expression of WNT2B in the human fetal kidney stroma but not in the organoids.

Conclusions:

This study supports the fidelity of kidney organoids as models of the developing kidney and affirms their potential in disease modelling and drug screening.

Authors

Alexander N. Combes#1,2+, Luke Zappia#2,3, Pei Xuan Er2, Alicia Oshlack2,3, Melissa H. Little1,2,3,4,+

1 Department of Anatomy & Neuroscience, University of Melbourne, VIC, Australia 2 Murdoch Children’s Research Institute, Flemington Rd, Parkville, VIC, Australia 3 School of Biosciences, The University of Melbourne, VIC, Australia 4 Department of Paediatrics, The University of Melbourne, VIC, Australia

# Equal contribution

+ Corresponding authors

Analysis

  • Quality control
    • Organoid Batch 1 - Quality control of the first batch of organoids containing three samples
    • Organoid 4 - Quality control of the second batch of organoids containing a single sample
    • Fetal kidney - Quality control of the Lindstrom fetal kidney dataset
  • Organoids analysis
  • Combined analysis
    • Integration - Integration of the organoids datasets and the Lindstrom fetal kidney dataset
    • Clustering - Clustering of the combined dataset
    • Nephron re-clustering - Re-clustering of the nephron lineage in the combined dataset
    • Figures - Figures for the combined analysis presented in the paper
  • Clustering crossover - Overlap in samples between clusters from different parts of the analysis
  • Methods - Methods describing the analysis

Licenses

The code in this analysis is covered by the MIT license and the written content on this website is covered by a Creative Commons CC-BY license.

The associated publication and the datasets used are covered by their respective licenses and usage agreements. Please refer to those sources for details.

Citations

The results of this analysis can be cited as:

Combes AN, Zappia L, Er PX, Oshlack A, Little MH. Single-cell analysis reveals congruence between kidney organoids and human fetal kidney. Genome Medicine. 2019. DOI: 10.1186/s13073-019-0615-0.

This website and the analysis code can be cited as:

Zappia, Luke, Combes, Alexander N., Er, Pei Xuan, Oshlack, Alicia, & Little, Melissa H. Combes organoid paper analysis code. Zenodo. 2019. DOI: 10.5281/zenodo.1960044.

This reproducible R Markdown analysis was created with workflowr 1.1.1