Transdifferentiation of pancreatic cells by loss of contact-mediated signaling

BMC Systems Biology

Lutz Brusch¹  Roland Zimm²  Walter de Back¹ 

[1] Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, 01062, Germany;Institute of Biotechnology, University of Helsinki, PO Box 56, Helsinki FIN-00014, Finland

关键词: Multicellular systems biology;    Mathematical model;    Islet cells;    Acinar cells;    Pancreas;    Reprogramming;    Intercellular communication;    Lineage conversion;   

Others  :  1142352
DOI  :  10.1186/1752-0509-7-77

 received in 2012-10-10, accepted in 2013-07-04,  发布年份 2013

【 摘 要 】

Background

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 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 β-cell neogenesis.

【 授权许可】

   
2013 de Back et al.; licensee BioMed Central Ltd.

【 图 表 】

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