Evidence map›Paper›PMID 33767186›Full record

ArticleNature communications2021

Dissection of two routes to naïve pluripotency using different kinase inhibitors.

Ana Martinez-Val, Cian J Lynch, Isabel Calvo, Pilar Ximénez-Embún, Fernando Garcia, Eduardo Zarzuela, Manuel Serrano, Javier Munoz

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Article
  2. A cross-talk between p16High senescence and cellular reprogramming.Clinical science (London, England : 1979) · 2026
    Review
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  11. p16Nature cell biology · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ana Martinez-ValProteomics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0002-8784-3822
Cian J LynchInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Isabel CalvoInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.ORCID http://orcid.org/0000-0003-4107-296X
Pilar Ximénez-EmbúnProteomics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0002-2582-9443
Fernando GarciaProteomics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Eduardo ZarzuelaProteomics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Manuel SerranoInstitute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.ORCID http://orcid.org/0000-0001-7177-9312
Javier MunozProteomics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. jmunozpe@cnio.es.ORCID http://orcid.org/0000-0003-3288-3496

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Embryonic stem cells (ESCs) can be maintained in the naïve state through inhibition of Mek1/2 and Gsk3 (2i). A relevant effect of 2i is the inhibition of Cdk8/19, which are negative regulators of the Mediator complex, responsible for the activity of enhancers. Inhibition of Cdk8/19 (Cdk8/19i) stimulates enhancers and, similar to 2i, stabilizes ESCs in the naïve state. Here, we use mass spectrometry to describe the molecular events (phosphoproteome, proteome, and metabolome) triggered by 2i and Cdk8/19i on ESCs. Our data reveal widespread commonalities between these two treatments, suggesting overlapping processes. We find that post-transcriptional de-repression by both 2i and Cdk8/19i might support the mitochondrial capacity of naive cells. However, proteome reprogramming in each treatment is achieved by different mechanisms. Cdk8/19i acts directly on the transcriptional machinery, activating key identity genes to promote the naïve program. In contrast, 2i stabilizes the naïve circuitry through, in part, de-phosphorylation of downstream transcriptional effectors.

Indexed as

AnimalsBenzamidesCell LineCyclin-Dependent Kinase 8Cyclin-Dependent KinasesDiphenylamineGlycogen Synthase Kinase 3MAP Kinase Kinase 1MAP Kinase Kinase 2Mass SpectrometryMiceMice, Inbred C57BLMitochondriaMouse Embryonic Stem CellsPhosphorylationPluripotent Stem CellsBenzamidesCDK19 protein, mouseCdk8 protein, mouseCyclin-Dependent Kinase 8Cyclin-Dependent KinasesDiphenylamineGlycogen Synthase Kinase 3Map2k1 protein, mouseMap2k2 protein, mouseMAP Kinase Kinase 1MAP Kinase Kinase 2mirdametinib

Identifiers

PMID33767186
PMCPMC7994667

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.