Dissection of two routes to naïve pluripotency using different kinase inhibitors

Research output: Contribution to journal › Journal article › Research › peer-review

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Dissection of two routes to naïve pluripotency using different kinase inhibitors. / Martinez-Val, Ana; Lynch, Cian J.; Calvo, Isabel; Ximénez-Embún, Pilar; Garcia, Fernando; Zarzuela, Eduardo; Serrano, Manuel; Munoz, Javier.

In: Nature Communications, Vol. 12, No. 1, 1863, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Martinez-Val, A, Lynch, CJ, Calvo, I, Ximénez-Embún, P, Garcia, F, Zarzuela, E, Serrano, M & Munoz, J 2021, 'Dissection of two routes to naïve pluripotency using different kinase inhibitors', Nature Communications, vol. 12, no. 1, 1863. https://doi.org/10.1038/s41467-021-22181-5

APA

Martinez-Val, A., Lynch, C. J., Calvo, I., Ximénez-Embún, P., Garcia, F., Zarzuela, E., Serrano, M., & Munoz, J. (2021). Dissection of two routes to naïve pluripotency using different kinase inhibitors. Nature Communications, 12(1), [1863]. https://doi.org/10.1038/s41467-021-22181-5

Vancouver

Martinez-Val A, Lynch CJ, Calvo I, Ximénez-Embún P, Garcia F, Zarzuela E et al. Dissection of two routes to naïve pluripotency using different kinase inhibitors. Nature Communications. 2021;12(1). 1863. https://doi.org/10.1038/s41467-021-22181-5

Author

Martinez-Val, Ana ; Lynch, Cian J. ; Calvo, Isabel ; Ximénez-Embún, Pilar ; Garcia, Fernando ; Zarzuela, Eduardo ; Serrano, Manuel ; Munoz, Javier. / Dissection of two routes to naïve pluripotency using different kinase inhibitors. In: Nature Communications. 2021 ; Vol. 12, No. 1.

Bibtex

@article{cb9fba3e41024bca96d5e7d08e4178b8,
title = "Dissection of two routes to na{\"i}ve pluripotency using different kinase inhibitors",
abstract = "Embryonic stem cells (ESCs) can be maintained in the na{\"i}ve 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 na{\"i}ve 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 na{\"i}ve program. In contrast, 2i stabilizes the na{\"i}ve circuitry through, in part, de-phosphorylation of downstream transcriptional effectors.",
author = "Ana Martinez-Val and Lynch, {Cian J.} and Isabel Calvo and Pilar Xim{\'e}nez-Emb{\'u}n and Fernando Garcia and Eduardo Zarzuela and Manuel Serrano and Javier Munoz",
year = "2021",
doi = "10.1038/s41467-021-22181-5",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Dissection of two routes to naïve pluripotency using different kinase inhibitors

AU - Martinez-Val, Ana

AU - Lynch, Cian J.

AU - Calvo, Isabel

AU - Ximénez-Embún, Pilar

AU - Garcia, Fernando

AU - Zarzuela, Eduardo

AU - Serrano, Manuel

AU - Munoz, Javier

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-22181-5

DO - 10.1038/s41467-021-22181-5

M3 - Journal article

C2 - 33767186

AN - SCOPUS:85103211523

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1863

ER -

ID: 261510398