The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids
Open accessAbstract
Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids surrounding hollow, amniotic-like cavities. GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. Tubules accumulate dextran and methotrexate transport cargoes, and express kidney injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of podocalyxin causes junctional organization defects in podocyte-like cells. Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst formation from kidney tubules. All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. Our findings establish a reproducible, versatile three-dimensional framework for human epithelial disease modelling and regenerative medicine applications.
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Cited by
Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184
Progress and potential in organoid research
Rossi, G., Manfrin, A., & Lutolf, M. P. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0051-9 · Cited by 1,182
Applications of CRISPR technologies in research and beyond
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Flow-enhanced vascularization and maturation of kidney organoids in vitro
Homan, K. A., Gupta, N., Kroll, K. T., Kolesky, D. B., Skylar-Scott, M., Miyoshi, T., Mau, D., Valerius, M. T., Ferrante, T., Bonventre, J. V., et al. (2019) · Nature Methods · doi:10.1038/s41592-019-0325-y · Cited by 939
Self-citationDisease modeling in stem cell-derived 3D organoid systems
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Metadata
- Authors
- Freedman, B. S., Brooks, C. R., Lam, A. Q., Fu, H., Morizane, R., Agrawal, V., Saad, A. F., Li, M. K., Hughes, M. R., Werff, R. V., Peters, D. T., Lu, J., Baccei, A., Siedlecki, A. M., Valerius, M. T., Musunuru, K., McNagny, K. M., Steinman, T. I., Zhou, J., Lerou, P. H., & Bonventre, J. V.
- Venue
- Nature Communications
- Published
- 2015-10-23
- Volume
- 6
- Issue
- 1
- Pages
- 8715-8715
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2176166968
- Cited by
- 780
- References
- 8
- FWCI
- 21.49
- Type
- journal article
- Language
- en
- Open access
- gold
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- The paper
- Freedman, B. S., Brooks, C. R., Lam, A. Q., Fu, H., Morizane, R., Agrawal, V., Saad, A. F., Li, M. K., Hughes, M. R., Werff, R. V., Peters, D. T., Lu, J., Baccei, A., Siedlecki, A. M., Valerius, M. T., Musunuru, K., McNagny, K. M., Steinman, T. I., Zhou, J., . . . Bonventre, J. V. (2015). Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nature Communications. https://doi.org/10.1038/ncomms9715
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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