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.
| Original language | English |
|---|---|
| Article number | 3 |
| Number of pages | 15 |
| Journal | Genome Medicine |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 23 Jan 2019 |
| Externally published | Yes |
Keywords
- Human kidney organoids
- Induced pluripotent cells
- Organoids
- Single-cell RNA sequencing
- Stem cell-derived models
Cite this
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Single-cell analysis reveals congruence between kidney organoids and human fetal kidney. / Combes, Alexander N.; Zappia, Luke; Er, Pei Xuan; Oshlack, Alicia; Little, Melissa H.
In: Genome Medicine, Vol. 11, No. 1, 3, 23.01.2019.Research output: Contribution to journal › Article › Research › peer-review
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: medicine in the post-genomic era
JF - Genome Medicine: medicine in the post-genomic era
SN - 1756-994X
IS - 1
M1 - 3
ER -