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Regulated Expression of pdx-1 Promotes In Vitro Differentiation of Insulin-Producing Cells From Embryonic Stem Cells
Open accessAbstract
Embryonic stem (ES) cells can differentiate into many cell types. Recent reports have shown that ES cells can differentiate into insulin-producing cells. However, the differentiation is not efficient enough to produce insulin-secreting cells for future therapeutic use. Pdx-1, a homeodomain-containing transcription factor, is a crucial regulator for pancreatic development. We established an ES cell line in which exogenous pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus. Using this cell line, we examined the effect of pdx-1 expression during in vitro differentiation via embryoid body formation. The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells. Immunohistochemical examination also revealed that insulin was highly produced in most of the differentiated ES cells. Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients.
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Cites
The protein CTCF is required for the enhancer blocking activity of vertebrate insulators
Bell, A. C., West, A. G., & Felsenfeld, G. (1999) · Cell · doi:10.1016/s0092-8674(00)81967-4 · Cited by 1,101
Cited by
Embryonic stem cell differentiation: emergence of a new era in biology and medicine
Keller, G. (2005) · Genes & Development · doi:10.1101/gad.1303605 · Cited by 1,151
The Potential of Amniotic Membrane/Amnion-Derived Cells for Regeneration of Various Tissues
Toda, A., Okabe, M., Yoshida, T., & Nikaido, T. (2007) · Journal of Pharmacological Sciences · doi:10.1254/jphs.cr0070034 · Cited by 386
Fujikawa, T., Oh, S.-H., Pi, L., Hatch, H. M., Shupe, T., & Petersen, B. E. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62488-1 · Cited by 317
Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes
Kaneto, H., Matsuoka, T.-A., Nakatani, Y., Kawamori, D., Miyatsuka, T., Matsuhisa, M., & Yamasaki, Y. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0640-x · Cited by 193
Oliver-Krasinski, J. M., Kasner, M. T., Yang, J., Crutchlow, M. F., Rustgi, A. K., Kaestner, K. H., & Stoffers, D. A. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37028 · Cited by 177
Metadata
- Authors
- Miyazaki, S., Yamato, E., & Miyazaki, J.-I.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-04-01
- Volume
- 53
- Issue
- 4
- Pages
- 1030-1037
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2101387801
- Cited by
- 244
- References
- 1
- FWCI
- 31.80
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Miyazaki, S., Yamato, E., & Miyazaki, J.-I. (2004). Regulated Expression of pdx-1 Promotes In Vitro Differentiation of Insulin-Producing Cells From Embryonic Stem Cells. Diabetes. https://doi.org/10.2337/diabetes.53.4.1030
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