PXD018694

PXD018694 is an original dataset announced via ProteomeXchange.

Title	MASS SPECTROMETRY ROADMAPS TO NAIVE PLURIPOTENCY
Description	Pluripotency can be maintained in the naïve state through manipulation of ERK and WNT signalling (2i), shielding embryonic stem cells (ESCs) from inductive cues. Alternatively, inhibiting CDK8/19 (CDK8/19i), a repressor of the Mediator co-activator complex, directly stimulates super-enhancer activity, and was recently shown to stabilize cells in a functional state that resembles naïve pluripotency. Naïve ESCs exhibit important epigenetic, transcriptional and metabolic features. However, our understanding on how these regulatory layers are inter-connected to promote the naive state is in progress. To fill this gap, here we used mass spectrometry to describe the dynamic molecular events (i.e. phosphoproteome, proteome and metabolome) executed by 2i and CDK8/19i, as they transition cell identity into naïve pluripotency. We observed rapid proteomic reprogramming, revealing widespread commonalities, and some important differences, between these two approaches, suggesting a largely over-lapping mechanism. CDK8/19i acts directly on the control of the transcriptional machinery, which elicits a rapid and direct activation of key identity genes including those that maintain the naïve program. Additional molecular changes in 2i are achieved by phosphorylation of critical downstream effectors that reinforce the naïve transcriptional circuitry while repressing factors from the more-differentiated formative and primed states. Comparing transcriptomic and proteomic changes, we found that post-transcriptional de-repression is a major feature of naïve pluripotency conferred by both 2i and CDK8/19i, and this may support the enhanced mitochondrial capacity of naive cells. Furthermore, at the level of metabolome, while 2i- and CDK8/19i-treated cells share similar aspects in one-carbon metabolism and beta-oxidation, in other regards they are divergent, a feature which may explain their differences in DNA methylation. These datasets provide a valuable resource for exploring the molecular mechanisms underlying pluripotency and cell identity transitions.
HostingRepository	PRIDE
AnnounceDate	2021-02-10
AnnouncementXML	Submission_2021-04-06_01:10:45.216.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ana Martinez-Val
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF; maXis

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-20 09:20:31	ID requested
1	2021-02-10 08:33:32	announced
⏵ 2	2021-04-06 01:10:46	announced	2021-04-06: Updated publication reference for PubMed record(s): 33767186.

Martinez-Val A, Lynch CJ, Calvo I, Xim, é, nez-Emb, ú, n P, Garcia F, Zarzuela E, Serrano M, Munoz J, ve pluripotency using different kinase inhibitors. Nat Commun, 12(1):1863(2021) [pubmed]

submitter keyword: Mouse Stem Cells, Proteomics, Phosphoproteomics

Javier Munoz
contact affiliation	Head of Proteomics Unit, CNIO, Madrid (Spain)
contact email	jmunozpe@cnio.es
lab head
Ana Martinez-Val
contact affiliation	Novo Nordisk Foundation Center for Protein Research
contact email	ana.mdval@cpr.ku.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018694
     1. Label: PRIDE project
     2. Name: MASS SPECTROMETRY ROADMAPS TO NAIVE PLURIPOTENCY