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

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