The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells
Open accessAbstract
Mouse embryonic stem (ES) cells differentiate into cells of all three primary germ layers including endodermal cells that produce insulin in vitro . We show that constitutive expression of Pax4 (Pax4 + ), and to a lesser extent Pdx1 (Pdx1 + ), affects the differentiation of ES cells and significantly promote the development of insulin-producing cells. In Pax4 overexpressing R1 ES cells, isl-1, ngn3, insulin, islet amyloid polypeptide, and glucose transporter 2 (Glut-2) mRNA levels increase significantly. The number of nestin-expressing (nestin+) cells also increases. Constitutive Pax4 expression combined with selection of nestin+ cells and histotypic culture conditions give rise to spheroids containing insulin-positive granules typical of embryonal and adult β cells. In response to glucose, Pax4 + and wild-type ES-derived cells release insulin. Transplantation of these cells into streptozotocin-treated diabetic mice results in a normalization of blood glucose levels. We conclude that constitutive expression of Pax4 in combination with histotypic cultivation facilitates ES cell differentiation into the pancreatic lineage, which leads to the formation of islet-like spheroid structures that produce increased levels of insulin.
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Cited by
Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells
Yasunaga, M., Tada, S., Torikai-Nishikawa, S., Nakano, Y., Okada, M., Jakt, L. M., Nishikawa, S., Chiba, T., Era, T., & Nishikawa, S.-I. (2005) · Nature Biotechnology · doi:10.1038/nbt1167 · Cited by 471
Duan, F. F., Liu, J. H., & March, J. C. (2015) · Diabetes · doi:10.2337/db14-0635 · Cited by 263
Molecular regulation of pancreatic β-cell mass development, maintenance, and expansion
Ackermann, A. M., & Gannon, M. (2007) · Journal of Molecular Endocrinology · doi:10.1677/jme-06-0053 · Cited by 262
Artifactual Insulin Release From Differentiated Embryonic Stem Cells
Hansson, M., Tonning, A., Frandsen, U., Petri, A., Rajagopal, J., Englund, M. C. O., Heller, R. S., Håkansson, J., Fleckner, J., Sköld, H. N., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.10.2603 · Cited by 225
Blyszczuk, P., Asbrand, C., Rozzo, A., Kania, G., St-onge, L., Rupnik, M., & Wobus, A. M. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041904pb · Cited by 110
Self-citation
Metadata
- Authors
- Blyszczuk, P., Czyz, J., Kania, G., Wagner, M., Roll, U., St-Onge, L., & Wobus, A. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-01-13
- Volume
- 100
- Issue
- 3
- Pages
- 998-1003
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2034224176
- Cited by
- 444
- References
- 37
- FWCI
- 50.77
- Type
- journal article
- Language
- en
- Open access
- green
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