Transdifferentiation of pancreatic cells by loss of contact-mediated signaling

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http://hdl.handle.net/10138/164361

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de Back , W , Zimm , R & Brusch , L 2013 , ' Transdifferentiation of pancreatic cells by loss of contact-mediated signaling ' BMC Systems Biology , vol. 7 , 77 . DOI: 10.1186/1752-0509-7-77

Title: Transdifferentiation of pancreatic cells by loss of contact-mediated signaling
Author: de Back, Walter; Zimm, Roland; Brusch, Lutz
Contributor: University of Helsinki, Institute of Biotechnology
Date: 2013-08-13
Language: eng
Number of pages: 11
Belongs to series: BMC Systems Biology
ISSN: 1752-0509
URI: http://hdl.handle.net/10138/164361
Abstract: Background: Replacement of dysfunctional beta-cells in the islets of Langerhans by transdifferentiation of pancreatic acinar cells has been proposed as a regenerative therapy for diabetes. Adult acinar cells spontaneously revert to a multipotent state upon tissue dissociation in vitro and can be stimulated to redifferentiate into beta-cells. Despite accumulating evidence that contact-mediated signals are involved, the mechanisms regulating acinar-to-islet cell transdifferentiation remain poorly understood. Results: In this study, we propose that the crosstalk between two contact-mediated signaling mechanisms, lateral inhibition and lateral stabilization, controls cell fate stability and transdifferentiation of pancreatic cells. Analysis of a mathematical model combining gene regulation with contact-mediated signaling reveals the multistability of acinar and islet cell fates. Inhibition of one or both modes of signaling results in transdifferentiation from the acinar to the islet cell fate, either by dedifferentiation to a multipotent state or by direct lineage switching. Conclusions: This study provides a theoretical framework to understand the role of contact-mediated signaling in pancreatic cell fate control that may help to improve acinar-to-islet cell transdifferentiation strategies for beta-cell neogenesis.
Subject: Lineage conversion
Intercellular communication
Reprogramming
Pancreas
Acinar cells
Islet cells
Mathematical model
Multicellular systems biology
E-CADHERIN
IN-VITRO
STEM-CELLS
REGENERATIVE MEDICINE
ACINAR-CELLS
BETA-CELLS
DIFFERENTIATION
EXPRESSION
NOTCH
PTF1A
114 Physical sciences
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