Transdifferentiation of pancreatic cells by loss of contact-mediated signaling

Show simple item record de Back, Walter Zimm, Roland Brusch, Lutz 2016-06-20T13:46:01Z 2016-06-20T13:46:01Z 2013-08-13
dc.identifier.citation de Back , W , Zimm , R & Brusch , L 2013 , ' Transdifferentiation of pancreatic cells by loss of contact-mediated signaling ' , BMC Systems Biology , vol. 7 , 77 .
dc.identifier.other PURE: 56319562
dc.identifier.other PURE UUID: afc18fb9-ab2e-4214-bf71-7523717360ce
dc.identifier.other WOS: 000323230900001
dc.identifier.other Scopus: 84882680826
dc.description.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. en
dc.format.extent 11
dc.language.iso eng
dc.relation.ispartof BMC Systems Biology
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Lineage conversion
dc.subject Intercellular communication
dc.subject Reprogramming
dc.subject Pancreas
dc.subject Acinar cells
dc.subject Islet cells
dc.subject Mathematical model
dc.subject Multicellular systems biology
dc.subject E-CADHERIN
dc.subject IN-VITRO
dc.subject STEM-CELLS
dc.subject ACINAR-CELLS
dc.subject BETA-CELLS
dc.subject EXPRESSION
dc.subject NOTCH
dc.subject PTF1A
dc.subject 114 Physical sciences
dc.title Transdifferentiation of pancreatic cells by loss of contact-mediated signaling en
dc.type Article
dc.contributor.organization Institute of Biotechnology
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1752-0509
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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