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

Alexander N Combes, Luke Zappia, Pei Xuan Er, Alicia Oshlack, Melissa H Little
Author Information
  1. Alexander N Combes: Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, VIC, Australia. alexander.combes@unimelb.edu.au.
  2. Luke Zappia: Murdoch Children's Research Institute, Melbourne, VIC, Australia.
  3. Pei Xuan Er: Murdoch Children's Research Institute, Melbourne, VIC, Australia.
  4. Alicia Oshlack: Murdoch Children's Research Institute, Melbourne, VIC, Australia.
  5. Melissa H Little: Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, VIC, Australia. melissa.little@mcri.edu.au. ORCID

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.
METHODS: 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.
RESULTS: Clusters in the combined dataset 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 were 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.
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.

Keywords

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Grants

  1. DK107344/NIDDK NIH HHS
  2. UH2 DK107344/NIDDK NIH HHS
  3. UH3 DK107344/NIDDK NIH HHS

MeSH Term

Cell Line
Cell Lineage
Glycoproteins
Humans
Induced Pluripotent Stem Cells
Kidney
Organoids
Single-Cell Analysis
Wnt Proteins

Chemicals

Glycoproteins
WNT2B protein, human
Wnt Proteins