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PXD023547-2

PXD023547 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDefining Essential Regulators of Naïve Human Pluripotent Cell Reprogramming
DescriptionDefining how human pluripotent cell identity is controlled and in particular how naïve pluripotency is acquired during cell reprogramming is crucial for the future applications of pluripotent stem cells. However, the regulatory pathways of naïve cell reprogramming remain incompletely understood. Here, we used genome-wide CRISPR-Cas9 screening to identify novel regulators of primed to naïve pluripotent stem cell reprogramming, including genes that are essential for reprogramming and genes that normally impede reprogramming and whose targeted deletion led to enhanced reprogramming. Integrated analysis defined specific chromatin complexes and signalling pathways as critical regulators of naïve reprogramming, and were largely distinct from regulators of somatic cell reprogramming. Mechanistically, PRC1.3 and PRDM14 are jointly required to transcriptionally repress developmental and gene regulatory factors to ensure naïve cell reprogramming. Additionally, small molecule inhibitors of reprogramming impediments increased the efficiency of naïve cell reprogramming, and are of practical benefit that can improve on current reprogramming methods. Taken together, we have identified novel regulators controlling the establishment of naïve pluripotency in human cells, which will open up new ways to exploit the full potential of pluripotent stem cells. These results also provide new insights into mechanisms that destabilise and reconfigure cell identity during cell state transitions.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:51:56.831.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterValar Nila Roamio Franklin
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmethylthiolated residue; monohydroxylated residue; deamidated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-01-12 06:25:07ID requested
12022-04-06 02:16:53announced
22023-11-14 08:51:57announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Pluripotent stem cells
embryonic stem cells
pluripotency
reprogramming
cell state
CRISPR
Polycomb
PRC1
Histone deacetylases
HDACs.
Contact List
Clive D' Santos
contact affiliationProteomics Lab Head, CRUK, University of cambridge
contact emailclivesdsantos@gmail.com
lab head
Valar Nila Roamio Franklin
contact affiliationResearch Assistant
contact emailValar.Franklin@cruk.cam.ac.uk
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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