Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice
- 17 November 2013
- journal article
- retracted article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 32 (1), 76-83
- https://doi.org/10.1038/nbt.2747
Abstract
Short-term treatment with cytokines reprograms acinar cells into beta cells and restores durable normoglycemia in diabetic mice. Reprogramming of pancreatic exocrine cells into cells resembling beta cells may provide a strategy for treating diabetes. Here we show that transient administration of epidermal growth factor and ciliary neurotrophic factor to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta-like cells are epigenetically reprogrammed, functional and glucose responsive, and they reinstate normal glycemic control for up to 248 d. The regenerative process depends on Stat3 signaling and requires a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. In contrast to previous work demonstrating in vivo conversion of acinar cells to beta-like cells by viral delivery of exogenous transcription factors, our approach achieves acinar-to-beta-cell reprogramming through transient cytokine exposure rather than genetic modification.Keywords
This publication has 53 references indexed in Scilit:
- Mouse digit tip regeneration is mediated by fate-restricted progenitor cellsProceedings of the National Academy of Sciences of the United States of America, 2011
- Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreasDevelopment, 2011
- Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreasBMC Developmental Biology, 2010
- Conversion of adult pancreatic α-cells to β-cells after extreme β-cell lossNature, 2010
- BMP signaling induces digit regeneration in neonatal miceDevelopment, 2010
- Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and functionProceedings of the National Academy of Sciences of the United States of America, 2009
- Comparative Aspects of Animal RegenerationAnnual Review of Cell and Developmental Biology, 2008
- Recovery from diabetes in mice by β cell regenerationJCI Insight, 2007
- Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regenerationJCI Insight, 2007
- Bridging the regeneration gap: genetic insights from diverse animal modelsNature Reviews Genetics, 2006