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dc.contributor.author
Kagawa, Harunobu
dc.contributor.author
Shimamoto, Ren
dc.contributor.author
Kim, Shin-Il
dc.contributor.author
Oceguera-Yanez, Fabian
dc.contributor.author
Yamamoto, Takuya
dc.contributor.author
Schroeder, Timm
dc.contributor.author
Woltjen, Knut
dc.date.accessioned
2019-02-18T16:11:48Z
dc.date.available
2019-02-11T04:30:50Z
dc.date.available
2019-02-18T16:11:48Z
dc.date.issued
2019-02-12
dc.identifier.issn
2213-6711
dc.identifier.other
10.1016/j.stemcr.2018.12.008
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/324081
dc.identifier.doi
10.3929/ethz-b-000324081
dc.description.abstract
During somatic cell reprogramming to induced pluripotent stem cells (iPSCs), fibroblasts undergo dynamic molecular changes, including a mesenchymal-to-epithelial transition (MET) and gain of pluripotency; processes that are influenced by Yamanaka factor stoichiometry. For example, in early reprogramming, high KLF4 levels are correlated with the induction of functionally undefined, transiently expressed MET genes. Here, we identified the cell-surface protein TROP2 as a marker for cells with transient MET induction in the high-KLF4 condition. We observed the emergence of cells expressing the pluripotency marker SSEA-1+ mainly from within the TROP2+ fraction. Using TROP2 as a marker in CRISPR/Cas9-mediated candidate screening of MET genes, we identified the transcription factor OVOL1 as a potential regulator of an alternative epithelial cell fate characterized by the expression of non-iPSC MET genes and low cell proliferation. Our study sheds light on how reprogramming factor stoichiometry alters the spectrum of intermediate cell fates, ultimately influencing reprogramming outcomes.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
iPSC
en_US
dc.subject
reprogramming
en_US
dc.subject
stoichiometry
en_US
dc.subject
KLF4
en_US
dc.subject
mesenchymal-to-epithelial transition
en_US
dc.subject
Tacstd2
en_US
dc.subject
TROP2
en_US
dc.subject
Ovol1
en_US
dc.subject
SSEA-1
en_US
dc.subject
CRISPR/Cas9
en_US
dc.title
OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2019-01-10
ethz.journal.title
Stem Cell Reports
ethz.journal.volume
12
en_US
ethz.journal.issue
2
en_US
ethz.pages.start
319
en_US
ethz.pages.end
332
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Berlin
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2019-02-11T04:30:57Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-02-18T16:12:06Z
ethz.rosetta.lastUpdated
2019-02-18T16:12:06Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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