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dc.contributor.authorPeñalosa-Ruiz, G
dc.contributor.authorBousgouni, V
dc.contributor.authorGerlach, JP
dc.contributor.authorWaarlo, S
dc.contributor.authorvan de Ven, JV
dc.contributor.authorVeenstra, TE
dc.contributor.authorSilva, JCR
dc.contributor.authorvan Heeringen, SJ
dc.contributor.authorBakal, C
dc.contributor.authorMulder, KW
dc.contributor.authorVeenstra, GJC
dc.date.accessioned2020-06-09T12:02:02Z
dc.date.issued2019-04
dc.identifier.citationStem cell reports, 2019, 12 (4), pp. 743 - 756
dc.identifier.issn2213-6711
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3711
dc.identifier.eissn2213-6711en_US
dc.identifier.doi10.1016/j.stemcr.2019.02.006en_US
dc.description.abstractDifferentiated cells are epigenetically stable, but can be reprogrammed to pluripotency by expression of the OSKM transcription factors. Despite significant effort, relatively little is known about the cellular requirements for reprogramming and how they affect the properties of induced pluripotent stem cells. We have performed high-content screening with small interfering RNAs targeting 300 chromatin-associated factors and extracted colony-level quantitative features. This revealed five morphological phenotypes in early reprogramming, including one displaying large round colonies exhibiting an early block of reprogramming. Using RNA sequencing, we identified transcriptional changes associated with these phenotypes. Furthermore, double knockdown epistasis experiments revealed that BRCA1, BARD1, and WDR5 functionally interact and are required for the DNA damage response. In addition, the mesenchymal-to-epithelial transition is affected in Brca1, Bard1, and Wdr5 knockdowns. Our data provide a resource of chromatin-associated factors in early reprogramming and underline colony morphology as an important high-dimensional readout for reprogramming quality.
dc.formatPrint-Electronic
dc.format.extent743 - 756
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectChromatin
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectDNA Damage
dc.subjectUbiquitin-Protein Ligases
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectTumor Suppressor Proteins
dc.subjectBRCA1 Protein
dc.subjectTranscription Factors
dc.subjectGene Expression Profiling
dc.subjectSignal Transduction
dc.subjectDNA Repair
dc.subjectPhenotype
dc.subjectEpithelial-Mesenchymal Transition
dc.subjectCellular Reprogramming
dc.titleWDR5, BRCA1, and BARD1 Co-regulate the DNA Damage Response and Modulate the Mesenchymal-to-Epithelial Transition during Early Reprogramming.
dc.typeJournal Article
dcterms.dateAccepted2019-02-14
rioxxterms.versionofrecord10.1016/j.stemcr.2019.02.006
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-04en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfStem cell reports
pubs.issue4
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.publication-statusPublished
pubs.volume12en_US
pubs.embargo.termsNot known
icr.researchteamDynamical Cell Systemsen_US
dc.contributor.icrauthorBakal, Christopheren
dc.contributor.icrauthorBousgouni, Paraskevien


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