Reprogramming of pancreatic exocrine cells AR42J into insulin-producing cells using mRNAs for Pdx1, Ngn3, and MafA transcription factors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F16%3A00059976" target="_blank" >RIV/00023001:_____/16:00059976 - isvavai.cz</a>
Result on the web
<a href="http://www.nature.com/mtna/journal/v5/n5/pdf/mtna201633a.pdf" target="_blank" >http://www.nature.com/mtna/journal/v5/n5/pdf/mtna201633a.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/mtna.2016.33" target="_blank" >10.1038/mtna.2016.33</a>
Alternative languages
Result language
angličtina
Original language name
Reprogramming of pancreatic exocrine cells AR42J into insulin-producing cells using mRNAs for Pdx1, Ngn3, and MafA transcription factors
Original language description
Direct reprogramming of pancreatic nonendocrine cells into insulin-producing beta-cells represents a promising approach for the treatment of insulin-dependent diabetes. However, its clinical application is limited by the potential for insertional mutagenesis associated with the viral vectors currently used for cell reprogramming. With the aim of developing a nonintegrative reprogramming strategy for derivation of insulin-producing cells, here, we evaluated a new approach utilizing synthetic messenger RNAs encoding reprogramming transcription factors. Administration of synthetic mRNAs encoding three key transcription regulators of beta-cell differentiation-Pdx1, Neurogenin3, and MafA-efficiently reprogrammed the pancreatic exocrine cells into insulin-producing cells. In addition to the insulin genes expression, the synthetic mRNAs also induced the expressions of genes important for proper pancreatic beta-cell function, including Sur1, Kir6.2, Pcsk1, and Pcsk2. Pretreating cells with the chromatin-modifying agent 5-Aza-2'-deoxycytidine further enhanced reprogramming efficiency, increasing the proportion of insulin-producing cells from 3.5 +/- 0.9 to 14.3 +/- 1.9% (n = 4). Moreover, 5-Aza-2'-deoxycytidine pretreatment enabled the reprogrammed cells to respond to glucose challenge with increased insulin secretion. In conclusion, our results support that the reprogramming of pancreatic exocrine cells into insulin-producing cells, induced by synthetic mRNAs encoding pancreatic transcription factors, represents a promising approach for cell-based diabetes therapy.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FB - Endocrinology, diabetology, metabolism, nutrition
OECD FORD branch
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Result continuities
Project
<a href="/en/project/NT12190" target="_blank" >NT12190: Insulin-producing cell lines generated from adult pancreatic cells for the treatment of diabetes</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular therapy-nucleic acids
ISSN
2162-2531
e-ISSN
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Volume of the periodical
5
Issue of the periodical within the volume
May 2016
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
"art. no. e320"
UT code for WoS article
000376427500001
EID of the result in the Scopus database
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