The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs
Open accessAbstract
The isolation of human induced pluripotent stem cells (iPSCs) offers a new strategy for modelling human disease. Recent studies have reported the derivation and differentiation of disease-specific human iPSCs. However, a key challenge in the field is the demonstration of disease-related phenotypes and the ability to model pathogenesis and treatment of disease in iPSCs. Familial dysautonomia (FD) is a rare but fatal peripheral neuropathy, caused by a point mutation in the IKBKAP gene involved in transcriptional elongation. The disease is characterized by the depletion of autonomic and sensory neurons. The specificity to the peripheral nervous system and the mechanism of neuron loss in FD are poorly understood owing to the lack of an appropriate model system. Here we report the derivation of patient-specific FD-iPSCs and the directed differentiation into cells of all three germ layers including peripheral neurons. Gene expression analysis in purified FD-iPSC-derived lineages demonstrates tissue-specific mis-splicing of IKBKAP in vitro. Patient-specific neural crest precursors express particularly low levels of normal IKBKAP transcript, suggesting a mechanism for disease specificity. FD pathogenesis is further characterized by transcriptome analysis and cell-based assays revealing marked defects in neurogenic differentiation and migration behaviour. Furthermore, we use FD-iPSCs for validating the potency of candidate drugs in reversing aberrant splicing and ameliorating neuronal differentiation and migration. Our study illustrates the promise of iPSC technology for gaining new insights into human disease pathogenesis and treatment.
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Cites
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009) · Nature Biotechnology · doi:10.1038/nbt.1529 · Cited by 3,620
Self-citationReprogramming of human somatic cells to pluripotency with defined factors
Park, I.-H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W., & Daley, G. Q. (2008) · Nature · doi:10.1038/nature06534 · Cited by 2,436
Disease-Specific Induced Pluripotent Stem Cells.
Park, I.-H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M. W., Cowan, C., Hochedlinger, K., & Daley, G. Q. (2008) · Cell · doi:10.1016/j.cell.2008.07.041 · Cited by 2,196
Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., Croft, G. F., Saphier, G., Leibel, R., Goland, R., et al. (2008) · Science · doi:10.1126/science.1158799 · Cited by 1,962
Efficient differentiation of human embryonic stem cells to definitive endoderm
D'Amour, K. A., Agulnick, A. D., Eliazer, S., Kelly, O. G., Kroon, E., & Baetge, E. E. (2005) · Nature Biotechnology · doi:10.1038/nbt1163 · Cited by 1,730
Soldner, F., Hockemeyer, D., Beard, C., Gao, Q., Bell, G. W., Cook, E. G., Hargus, G., Blak, A., Cooper, O., Mitalipova, M., et al. (2009) · Cell · doi:10.1016/j.cell.2009.02.013 · Cited by 1,549
Induced pluripotent stem cells from a spinal muscular atrophy patient
Ebert, A. D., Yu, J., Rose, F. F., Mattis, V. B., Lorson, C. L., Thomson, J. A., & Svendsen, C. N. (2009) · Nature · doi:10.1038/nature07677 · Cited by 1,441
Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000305204.97355.0d · Cited by 1,174
Cited by
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525
Modelling schizophrenia using human induced pluripotent stem cells
Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., et al. (2011) · Nature · doi:10.1038/nature09915 · Cited by 1,375
Marchetto, M. C. N., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y., Chen, G., Gage, F. H., & Muotri, A. R. (2010) · Cell · doi:10.1016/j.cell.2010.10.016 · Cited by 1,329
Patient-Specific Induced Pluripotent Stem-Cell Models for Long-QT Syndrome
Moretti, A., Bellin, M., Welling, A., Jung, C. B., Lam, J. T., Bott-Flügel, L., Dorn, T., Goedel, A., Höhnke, C., Hofmann, F., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0908679 · Cited by 1,251
Shi, Y., Kirwan, P., & Livesey, F. J. (2012) · Nature Protocols · doi:10.1038/nprot.2012.116 · Cited by 972
Metadata
- Authors
- Lee, G., Papapetrou, E. P., Kim, H., Chambers, S. M., Tomishima, M. J., Fasano, C. A., Ganat, Y. M., Menon, J., Shimizu, F., Viale, A., Tabar, V., Sadelain, M., & Studer, L.
- Venue
- Nature
- Published
- 2009-08-19
- Volume
- 461
- Issue
- 7262
- Pages
- 402-406
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2126774748
- Cited by
- 867
- References
- 30
- FWCI
- 43.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Lee, G., Papapetrou, E. P., Kim, H., Chambers, S. M., Tomishima, M. J., Fasano, C. A., Ganat, Y. M., Menon, J., Shimizu, F., Viale, A., Tabar, V., Sadelain, M., & Studer, L. (2009). Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature. https://doi.org/10.1038/nature08320
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