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AuthorKrüger, Janadc.contributor.author
AuthorBreunig, Markusdc.contributor.author
AuthorPasquini, Lino Pascaldc.contributor.author
AuthorMorawe, Mareendc.contributor.author
AuthorGroß, Alexanderdc.contributor.author
AuthorArnold, Frankdc.contributor.author
AuthorRussell, Ronandc.contributor.author
AuthorSeufferlein, Thomasdc.contributor.author
AuthorAzoitei, Nineldc.contributor.author
AuthorKestler, Hans A.dc.contributor.author
AuthorJulier, Céciledc.contributor.author
AuthorHeller, Sandradc.contributor.author
AuthorHohwieler, Meikedc.contributor.author
AuthorKleger, Alexanderdc.contributor.author
EditorRuss, Holgerdc.contributor.editor
Date of accession2022-05-30T14:00:45Zdc.date.accessioned
Available in OPARU since2022-05-30T14:00:45Zdc.date.available
Date of first publication2022-02-08dc.date.issued
AbstractHuman pluripotent stem cells, with their ability to proliferate indefinitely and to differentiate into virtually all cell types of the human body, provide a novel resource to study human development and to implement relevant disease models. Here, we employed a human pancreatic differentiation platform complemented with an shRNA screen in human pluripotent stem cells (PSCs) to identify potential drivers of early endoderm and pancreatic development. Deep sequencing followed by abundancy ranking pinpointed six top hit genes potentially associated with either improved or impaired endodermal differentiation, which were selected for functional validation in CRISPR-Cas9 mediated knockout (KO) lines. Upon endoderm differentiation (DE), particularly the loss of SLC22A1 and DSC2 led to impaired differentiation efficiency into CXCR4/KIT-positive DE cells. qPCR analysis also revealed changes in differentiation markers CXCR4, FOXA2, SOX17, and GATA6. Further differentiation of PSCs to the pancreatic progenitor (PP) stage resulted in a decreased proportion of PDX1/NKX6-1-positive cells in SLC22A1 KO lines, and in DSC2 KO lines when differentiated under specific culture conditions. Taken together, our study reveals novel genes with potential roles in early endodermal development.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY 4.0 Internationaldc.rights
Link to license texthttps://creativecommons.org/licenses/by/4.0/dc.rights.uri
Keywordstem cellsdc.subject
Keywordpancreatic developmentdc.subject
Keyworddefinitive endodermdc.subject
KeywordshRNAdc.subject
KeywordCATION TRANSPORTER 1dc.subject
KeywordIN-VITROdc.subject
KeywordEXPRESSIONdc.subject
KeywordDESMOCOLLIN-2dc.subject
KeywordCARDIOMYOPATHYdc.subject
KeywordCARCINOMAdc.subject
KeywordMOUSEdc.subject
Dewey Decimal GroupDDC 570 / Life sciencesdc.subject.ddc
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHStem cellsdc.subject.mesh
MeSHPluripotent stem cellsdc.subject.mesh
MeSHRNAdc.subject.mesh
MeSHMutationdc.subject.mesh
MeSHOrganic cation transport proteinsdc.subject.mesh
MeSHCardiomyopathiesdc.subject.mesh
MeSHGenomicsdc.subject.mesh
TitleFunctional genomic screening in human pluripotent stem cells reveals new roadblocks in early pancreatic endoderm formationdc.title
Resource typeWissenschaftlicher Artikeldc.type
SWORD Date2022-03-23T03:16:47Zdc.date.updated
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-43260dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-43336-5dc.identifier.urn
GNDKrebs <Medizin>dc.subject.gnd
GNDBlutstammzelledc.subject.gnd
GNDPluripotente Stammzelledc.subject.gnd
GNDRNSdc.subject.gnd
GNDGenomikdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionUKU. Klinik für Innere Medizin Iuulm.affiliationSpecific
InstitutionInstitut für Medizinische Systembiologieuulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
In cooperation withUniversité de Parisuulm.cooperation
DOI of original publication10.3390/cells11030582dc.relation1.doi
Source - Title of sourceCellssource.title
Source - Place of publicationMDPIsource.publisher
Source - Volume11source.volume
Source - Issue3source.issue
Source - Year2022source.year
Source - Article number582source.articleNumber
Source - eISSN2073-4409source.identifier.eissn
CommunityUniversität Ulm / Medizinuulm.community
WoS000758953300001uulm.identifier.wos
Bibliographyuulmuulm.bibliographie
Is Supplemented Byhttps://www.mdpi.com/article/10.3390/cells11030582/s1dc.relation.isSupplementedBy
DFG project uulmGRK 2254 / HEIST / Heterogenität und Evolution in soliden Tumoren (HEIST) / DFG / 288342734uulm.projectDFG
DFG project uulmMonogenetische Formen des juvenil sich manifestierenden Diabetes: neue Schritte in Richtung β-Zellentwicklung, -funktion und -überleben / DFG / 406674944 [KL 2544/5-1]uulm.projectDFG
DFG project uulmZelluläre Plastizität im Pankreas - vom Krankheitsmodell über Gewebserneuerung zur personalisierten Medizin / DFG / 426789149 [KL 2544/6-1]uulm.projectDFG
Project uulmInternational PhD Programme in Molecular Medicine / IGradU, Universität Ulmuulm.projectOther
xmlui.metadata.uulm.OAfundingOpen-Access-Förderung durch die Medizinische Fakultät der Universität Ulmuulm.OAfunding
xmlui.metadata.uulm.OAfundingGefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491116205uulm.OAfunding


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