TY - JOUR
T1 - Single-cell analysis reveals congruence between kidney organoids and human fetal kidney
AU - Combes, Alexander N.
AU - Zappia, Luke
AU - Er, Pei Xuan
AU - Oshlack, Alicia
AU - Little, Melissa H.
PY - 2019/1/23
Y1 - 2019/1/23
N2 - 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.
AB - 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.
KW - Human kidney organoids
KW - Induced pluripotent cells
KW - Organoids
KW - Single-cell RNA sequencing
KW - Stem cell-derived models
UR - http://www.scopus.com/inward/record.url?scp=85060403090&partnerID=8YFLogxK
U2 - 10.1186/s13073-019-0615-0
DO - 10.1186/s13073-019-0615-0
M3 - Article
C2 - 30674341
AN - SCOPUS:85060403090
VL - 11
JO - Genome Medicine
JF - Genome Medicine
SN - 1756-994X
IS - 1
M1 - 3
ER -