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Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function
Open accessAbstract
Neurog3 (Neurogenin 3 or Ngn3) is both necessary and sufficient to induce endocrine islet cell differentiation from embryonic pancreatic progenitors. Since robust Neurog3 expression has not been detected in hormone-expressing cells, Neurog3 is used as an endocrine progenitor marker and regarded as dispensable for the function of differentiated islet cells. Here we used 3 independent lines of Neurog3 knock-in reporter mice and mRNA/protein-based assays to examine Neurog3 expression in hormone-expressing islet cells. Neurog3 mRNA and protein are detected in hormone-producing cells at both embryonic and adult stages. Significantly, inactivating Neurog3 in insulin -expressing β cells at embryonic stages or in Pdx1 -expressing islet cells in adults impairs endocrine function, a phenotype that is accompanied by reduced expression of several Neurog3 target genes that are essential for islet cell differentiation, maturation, and function. These findings demonstrate that Neurog3 is required not only for initiating endocrine cell differentiation, but also for promoting islet cell maturation and maintaining islet function.
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Citations
Cited by
Pancreatic β Cell Dedifferentiation as a Mechanism of Diabetic β Cell Failure
Talchai, C., Xuan, S., Lin, H. V., Sussel, L., & Accili, D. (2012) · Cell · doi:10.1016/j.cell.2012.07.029 · Cited by 1,415
Kopp, J. L., Dubois, C. L., Schaffer, A. E., Hao, E., Shih, H. P., Seymour, P. A., Ma, J., & Sander, M. (2011) · Development · doi:10.1242/dev.056499 · Cited by 469
Self-citationPancreatic β Cell Dedifferentiation in Diabetes and Redifferentiation following Insulin Therapy
Wang, Z., York, N. W., Nichols, C. G., & Remedi, M. S. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.010 · Cited by 406
Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes
Cheng, C.-W., Villani, V., Buono, R., Wei, M., Kumar, S., Yilmaz, O. H., Cohen, P., Sneddon, J. B., Perin, L., & Longo, V. D. (2017) · Cell · doi:10.1016/j.cell.2017.01.040 · Cited by 331
Benner, C., van der Meulen, T., Cacéres, E., Tigyi, K., Donaldson, C. J., & Huising, M. O. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-620 · Cited by 302
Metadata
- Authors
- Wang, S., Jensen, J. N., Seymour, P. A., Hsu, W., Dor, Y., Sander, M., Magnuson, M. A., Serup, P., & Gu, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-06-16
- Volume
- 106
- Issue
- 24
- Pages
- 9715-9720
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2131145532
- Cited by
- 160
- References
- 0
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- green
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- Wang, S., Jensen, J. N., Seymour, P. A., Hsu, W., Dor, Y., Sander, M., Magnuson, M. A., Serup, P., & Gu, G. (2009). Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0904247106
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