Long-term persistence and development of induced pancreatic beta cells generated by lineage conversion of acinar cells
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Li, Weida
Cavelti-Weder, Claudia
Zhang, Yinying
Clement, Kendell
Donovan, Scott
Gonzalez, Gabriel
Zhu, Jiang
Stemann, Marianne
Xu, Ke
Hashimoto, Tatsu
Yamada, Takatsugu
Nakanishi, Mio
Zhang, Yuemei
Zeng, Samuel
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https://doi.org/10.1038/nbt.3082Metadata
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Li, Weida, Claudia Cavelti-Weder, Yinying Zhang, Kendell Clement, Scott Donovan, Gabriel Gonzalez, Jiang Zhu, et al. 2014. “Long-Term Persistence and Development of Induced Pancreatic Beta Cells Generated by Lineage Conversion of Acinar Cells.” Nature Biotechnology 32 (12) (November 17): 1223–1230. doi:10.1038/nbt.3082.Abstract
Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet–like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for >1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:42658794
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