The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein
Open accessAbstract
Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which regulates chloride and water transport across all epithelia and affects multiple organs, including the lungs. Here we report an in vitro directed differentiation protocol for generating functional CFTR-expressing airway epithelia from human embryonic stem cells. Carefully timed treatment by exogenous growth factors that mimic endoderm developmental pathways in vivo followed by air-liquid interface culture results in maturation of patches of tight junction–coupled differentiated airway epithelial cells that demonstrate active CFTR transport function. As a proof of concept, treatment of CF patient induced pluripotent stem cell–derived epithelial cells with a small-molecule compound to correct for the common CF processing mutation resulted in enhanced plasma membrane localization of mature CFTR protein. Our study provides a method for generating patient-specific airway epithelial cells for disease modeling and in vitro drug testing.
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Cites
Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809
Van Goor, F., Hadida, S., Grootenhuis, P. D. J., Burton, B., Stack, J. H., Straley, K. S., Decker, C. J., Miller, M., McCartney, J., Olson, E. R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105787108 · Cited by 1,088
Vertebrate Endoderm Development and Organ Formation
Zorn, A. M., & Wells, J. M. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113344 · Cited by 812
Cited by
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196
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
Long‐term expanding human airway organoids for disease modeling
Sachs, N., Papaspyropoulos, A., Zomer‐van Ommen, D. D., Heo, I., Böttinger, L., Klay, D., Weeber, F., Huelsz‐Prince, G., Iakobachvili, N., Amatngalim, G. D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100300 · Cited by 1,082
A functional CFTR assay using primary cystic fibrosis intestinal organoids
Dekkers, J. F., Wiegerinck, C. L., de Jonge, H. R., Bronsveld, I., Janssens, H. M., de Winter-de Groot, K. M., Brandsma, A. M., de Jong, N. W. M., Bijvelds, M. J. C., Scholte, B. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3201 · Cited by 999
Metadata
- Authors
- Wong, A. P., Bear, C. E., Chin, S., Pasceri, P., Thompson, T. O., Huan, L.-J., Ratjen, F., Ellis, J., & Rossant, J.
- Venue
- Nature Biotechnology
- Published
- 2012-08-26
- Volume
- 30
- Issue
- 9
- Pages
- 876-882
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2076312582
- Cited by
- 424
- References
- 2
- FWCI
- 11.97
- Type
- journal article
- Language
- en
- Open access
- green
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- Wong, A. P., Bear, C. E., Chin, S., Pasceri, P., Thompson, T. O., Huan, L.-J., Ratjen, F., Ellis, J., & Rossant, J. (2012). Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein. Nature Biotechnology. https://doi.org/10.1038/nbt.2328
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