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 and Javier Munoz ()
Additional contact information
Ana Martinez-Val: Spanish National Cancer Research Centre (CNIO)
Cian J. Lynch: Barcelona Institute of Science and Technology (BIST)
Isabel Calvo: Barcelona Institute of Science and Technology (BIST)
Pilar Ximénez-Embún: Spanish National Cancer Research Centre (CNIO)
Fernando Garcia: Spanish National Cancer Research Centre (CNIO)
Eduardo Zarzuela: Spanish National Cancer Research Centre (CNIO)
Manuel Serrano: Barcelona Institute of Science and Technology (BIST)
Javier Munoz: Spanish National Cancer Research Centre (CNIO)

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22181-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22181-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22181-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().