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dc.contributor.author
Haellman, Viktor
dc.contributor.author
Saxena, Pratik
dc.contributor.author
Jianga, Yanrui
dc.contributor.author
Fussenegger, Martin
dc.date.accessioned
2021-06-17T11:06:11Z
dc.date.available
2021-04-02T02:51:00Z
dc.date.available
2021-04-20T11:05:06Z
dc.date.available
2021-06-17T11:06:11Z
dc.date.issued
2021-05
dc.identifier.issn
1096-7176
dc.identifier.issn
1096-7184
dc.identifier.other
10.1016/j.ymben.2021.03.009
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/477347
dc.identifier.doi
10.3929/ethz-b-000477347
dc.description.abstract
Advances in synthetic biology have enabled robust control of cell behavior by using tunable genetic circuits to regulate gene expression in a ligand-dependent manner. Such circuits can be used to direct the differentiation of pluripotent stem cells (PSCs) towards desired cell types, but rational design of synthetic gene circuits in PSCs is challenging due to the variable intracellular environment. Here, we provide a framework for implementing synthetic gene switches in PSCs based on combinations of tunable transcriptional, structural, and posttranslational elements that can be engineered as required, using the vanillic acid-controlled transcriptional activator (VanA) as a model system. We further show that the VanA system can be multiplexed with the well-established reverse tetracycline-controlled transcriptional activator (rtTA) system to enable independent control of the expression of different transcription factors in human induced PSCs in order to enhance lineage specification towards early pancreatic progenitors. This work represents a first step towards standardizing the design and construction of synthetic gene switches for building robust gene-regulatory networks to guide stem cell differentiation towards a desired cell fate.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Synthetic biology
en_US
dc.subject
Gene switch
en_US
dc.subject
Pluripotent stem cells
en_US
dc.subject
HHEX
en_US
dc.subject
TGIF2
en_US
dc.subject
Pancreatic progenitors
en_US
dc.title
Rational design and optimization of synthetic gene switches for controlling cell-fate decisions in pluripotent stem cells
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2021-03-17
ethz.journal.title
Metabolic Engineering
ethz.journal.volume
65
en_US
ethz.journal.abbreviated
Metab Eng
ethz.pages.start
99
en_US
ethz.pages.end
110
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
Electrogenetics - Shaping Electrogenetic Interfaces for Closed-Loop Voltage-Controlled Gene Expression
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Amsterdam
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
en_US
ethz.grant.agreementno
785800
ethz.grant.fundername
EC
ethz.grant.funderDoi
10.13039/501100000780
ethz.grant.program
H2020
ethz.date.deposited
2021-04-02T02:51:05Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-04-20T11:05:23Z
ethz.rosetta.lastUpdated
2022-03-29T08:50:09Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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