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

Genome Med. 2019 Jan 23;11(1):3. doi: 10.1186/s13073-019-0615-0.

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: Human kidney organoids; Induced pluripotent cells; Organoids; Single-cell RNA sequencing; Stem cell-derived models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Lineage
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Kidney / cytology*
  • Kidney / embryology
  • Organoids / cytology*
  • Organoids / metabolism
  • Single-Cell Analysis
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism

Substances

  • Glycoproteins
  • WNT2B protein, human
  • Wnt Proteins