Plasticity of Adult Human Pancreatic Duct Cells by Neurogenin3-mediated Reprogramming

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 May 19

PMID 22606327

Citations 29

Authors

Nathalie Swales

Geert A Martens

Stefan Bonne

Yves Heremans

Rehannah Borup

Mark Van de Casteele

Zhidong Ling

Daniel Pipeleers

Philippe Ravassard

Finn Nielsen

Jorge Ferrer

Harry Heimberg

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it.

Methods: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming.

Results: Ngn3 stimulates duct cells to express a focused set of genes that are characteristic for islet endocrine cells and/or neural tissues. This neuro-endocrine shift however, is incomplete with less than 10% of full duct-to-endocrine reprogramming achieved. Transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1.

Conclusions/interpretation: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes.

Citing Articles

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Vakilian M, Hmadcha A, Soria B, Ghaedi K In Vitro Cell Dev Biol Anim. 2021; 57(6):587-597.

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Small Molecule-Induced Pancreatic β-Like Cell Development: Mechanistic Approaches and Available Strategies.

Thakur G, Lee H, Jeon R, Lee S, Rho G Int J Mol Sci. 2020; 21(7).

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Highly efficient ex vivo lentiviral transduction of primary human pancreatic exocrine cells.

Balak J, de Graaf N, Zaldumbide A, Rabelink T, Hoeben R, de Koning E Sci Rep. 2019; 9(1):15870.

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Reprogramming Cells to Make Insulin.

McKimpson W, Accili D J Endocr Soc. 2019; 3(6):1214-1226.

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