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dc.contributor.author
Saxena, Pratik
dc.contributor.author
Heng, Boon C.
dc.contributor.author
Bai, Peng
dc.contributor.author
Folcher, Marc
dc.contributor.author
Zulewski, Henryk
dc.contributor.author
Fussenegger, Martin
dc.date.accessioned
2018-09-06T13:52:03Z
dc.date.available
2017-06-12T04:22:40Z
dc.date.available
2018-09-06T13:52:03Z
dc.date.issued
2016
dc.identifier.other
10.1038/ncomms11247
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/115280
dc.identifier.doi
10.3929/ethz-b-000115280
dc.description.abstract
Synthetic biology has advanced the design of standardized transcription control devices that programme cellular behaviour. By coupling synthetic signalling cascade- and transcription factor-based gene switches with reverse and differential sensitivity to the licensed food additive vanillic acid, we designed a synthetic lineage-control network combining vanillic acid-triggered mutually exclusive expression switches for the transcription factors Ngn3 (neurogenin 3; OFF-ON-OFF) and Pdx1 (pancreatic and duodenal homeobox 1; ON-OFF-ON) with the concomitant induction of MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; OFF-ON). This designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3, Pdx1 and MafA variants is able to programme human induced pluripotent stem cells (hIPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics are comparable to human pancreatic islets. Synthetic lineage-control networks may provide the missing link to genetically programme somatic cells into autologous cell phenotypes for regenerative medicine.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2016-04-11
ethz.journal.title
Nature Communications
ethz.journal.volume
7
en_US
ethz.pages.start
11247
en_US
ethz.size
14 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
007044158
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03694 - Fussenegger, Martin / Fussenegger, Martin
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::03694 - Fussenegger, Martin / Fussenegger, Martin
ethz.date.deposited
2017-06-12T04:26:09Z
ethz.source
ECIT
ethz.identifier.importid
imp59365450485b757470
ethz.ecitpid
pub:177105
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-13T11:19:27Z
ethz.rosetta.lastUpdated
2019-02-03T05:25:52Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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