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ZMYM2 inhibits NANOG-mediated reprogramming

Background: NANOG is a homeodomain-containing transcription factor which forms one of the hubs in the pluripotency network and plays a key role in the reprogramming of somatic cells and epiblast stem cells to naïve pluripotency.  Studies have found that NANOG has many interacting partners and some o...

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Autores principales: Lawrence, Moyra, Theunissen, Thorold W., Lombard, Patrick, Adams, David J., Silva, José C. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640293/
https://www.ncbi.nlm.nih.gov/pubmed/31363497
http://dx.doi.org/10.12688/wellcomeopenres.15250.1
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author Lawrence, Moyra
Theunissen, Thorold W.
Lombard, Patrick
Adams, David J.
Silva, José C. R.
author_facet Lawrence, Moyra
Theunissen, Thorold W.
Lombard, Patrick
Adams, David J.
Silva, José C. R.
author_sort Lawrence, Moyra
collection PubMed
description Background: NANOG is a homeodomain-containing transcription factor which forms one of the hubs in the pluripotency network and plays a key role in the reprogramming of somatic cells and epiblast stem cells to naïve pluripotency.  Studies have found that NANOG has many interacting partners and some of these were shown to play a role in its ability to mediate reprogramming. In this study, we set out to analyse the effect of NANOG interactors on the reprogramming process. Methods: Epiblast stem cells and somatic cells were reprogrammed to naïve pluripotency using MEK/ERK inhibitor PD0325901, GSK3β inhibitor CHIR99021 and Leukaemia Inhibitory Factor (together termed 2i Plus LIF). Zmym2 was knocked out using the CRISPR/Cas9 system or overexpressed using the PiggyBac system. Reprogramming was quantified after ZMYM2 deletion or overexpression, in diverse reprogramming systems. In addition, embryonic stem cell self renewal was quantified in differentiation assays after ZMYM2 removal or overexpression. Results: In this work, we identified ZMYM2/ZFP198, which physically associates with NANOG as a key negative regulator of NANOG-mediated reprogramming of both epiblast stem cells and somatic cells. In addition, ZMYM2 impairs the self renewal of embryonic stem cells and its overexpression promotes differentiation. Conclusions: We propose that ZMYM2 curtails NANOG’s actions during the reprogramming of both somatic cells and epiblast stem cells and impedes embryonic stem cell self renewal, promoting differentiation.
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spelling pubmed-66402932019-07-29 ZMYM2 inhibits NANOG-mediated reprogramming Lawrence, Moyra Theunissen, Thorold W. Lombard, Patrick Adams, David J. Silva, José C. R. Wellcome Open Res Research Article Background: NANOG is a homeodomain-containing transcription factor which forms one of the hubs in the pluripotency network and plays a key role in the reprogramming of somatic cells and epiblast stem cells to naïve pluripotency.  Studies have found that NANOG has many interacting partners and some of these were shown to play a role in its ability to mediate reprogramming. In this study, we set out to analyse the effect of NANOG interactors on the reprogramming process. Methods: Epiblast stem cells and somatic cells were reprogrammed to naïve pluripotency using MEK/ERK inhibitor PD0325901, GSK3β inhibitor CHIR99021 and Leukaemia Inhibitory Factor (together termed 2i Plus LIF). Zmym2 was knocked out using the CRISPR/Cas9 system or overexpressed using the PiggyBac system. Reprogramming was quantified after ZMYM2 deletion or overexpression, in diverse reprogramming systems. In addition, embryonic stem cell self renewal was quantified in differentiation assays after ZMYM2 removal or overexpression. Results: In this work, we identified ZMYM2/ZFP198, which physically associates with NANOG as a key negative regulator of NANOG-mediated reprogramming of both epiblast stem cells and somatic cells. In addition, ZMYM2 impairs the self renewal of embryonic stem cells and its overexpression promotes differentiation. Conclusions: We propose that ZMYM2 curtails NANOG’s actions during the reprogramming of both somatic cells and epiblast stem cells and impedes embryonic stem cell self renewal, promoting differentiation. F1000 Research Limited 2019-06-06 /pmc/articles/PMC6640293/ /pubmed/31363497 http://dx.doi.org/10.12688/wellcomeopenres.15250.1 Text en Copyright: © 2019 Lawrence M et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lawrence, Moyra
Theunissen, Thorold W.
Lombard, Patrick
Adams, David J.
Silva, José C. R.
ZMYM2 inhibits NANOG-mediated reprogramming
title ZMYM2 inhibits NANOG-mediated reprogramming
title_full ZMYM2 inhibits NANOG-mediated reprogramming
title_fullStr ZMYM2 inhibits NANOG-mediated reprogramming
title_full_unstemmed ZMYM2 inhibits NANOG-mediated reprogramming
title_short ZMYM2 inhibits NANOG-mediated reprogramming
title_sort zmym2 inhibits nanog-mediated reprogramming
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640293/
https://www.ncbi.nlm.nih.gov/pubmed/31363497
http://dx.doi.org/10.12688/wellcomeopenres.15250.1
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