PXD023547-1

PXD023547 is an original dataset announced via ProteomeXchange.

Title	Defining Essential Regulators of Naïve Human Pluripotent Cell Reprogramming
Description	Defining 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.
HostingRepository	PRIDE
AnnounceDate	2022-04-06
AnnouncementXML	Submission_2022-04-06_02:16:53.606.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valar Nila Roamio Franklin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-12 06:25:07	ID requested
⏵ 1	2022-04-06 02:16:53	announced
2	2023-11-14 08:51:57	announced	2023-11-14: Updated project metadata.

10.1126/SCIADV.ABK0013;

submitter keyword: Pluripotent stem cells

embryonic stem cells

pluripotency

reprogramming

cell state

CRISPR

Polycomb

PRC1

Histone deacetylases

HDACs.

Clive D' Santos
contact affiliation	Proteomics Lab Head, CRUK, University of cambridge
contact email	clivesdsantos@gmail.com
lab head
Valar Nila Roamio Franklin
contact affiliation	Research Assistant
contact email	Valar.Franklin@cruk.cam.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/04/PXD023547

PRIDE project URI

• PRIDE
  1. PXD023547
     1. Label: PRIDE project
     2. Name: Defining Essential Regulators of Naïve Human Pluripotent Cell Reprogramming