Nephron progenitor commitment is a stochastic process influenced by cell migration
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.
Citation
@article{t lawlor2019,
author = {T Lawlor, Kynan and Zappia, Luke and Lefevre, James and
Park, Joo-Seop and A Hamilton, Nicholas and Oshlack, Alicia and H
Little, Melissa and Nicholas Combes, Alexander},
title = {Nephron Progenitor Commitment Is a Stochastic Process
Influenced by Cell Migration},
journal = {eLife},
volume = {8},
pages = {e41156},
date = {2019-01-01},
url = {https://lazappi.id.au/publications/2019-lawlor-nephron-commitment},
doi = {10.7554/eLife.41156},
issn = {2050-084X},
langid = {en},
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.}
}