Dataset Information

Transdifferentiation of pancreatic cells by loss of contact-mediated signaling.

ABSTRACT:

Background

Replacement of dysfunctional ?-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 ?-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 ?-cell neogenesis.

SUBMITTER: de Back W

PROVIDER: S-EPMC3751562 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Transdifferentiation of pancreatic cells by loss of contact-mediated signaling.

de Back Walter W Zimm Roland R Brusch Lutz L

BMC systems biology 20130813

<h4>Background</h4>Replacement of dysfunctional β-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 β-cells. Despite accumulating evidence that contact-mediated signals are involved, the mechanisms regulating acinar-to-islet cell transdifferentiation remain poorly ...[more]

PMID: 23938152

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Dataset Information

Transdifferentiation of pancreatic cells by loss of contact-mediated signaling.

Background

Results

Conclusions

Publications

Transdifferentiation of pancreatic cells by loss of contact-mediated signaling.

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