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Succinate as a New Actor in Pluripotency and Early Development?
Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several interm...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325148/ https://www.ncbi.nlm.nih.gov/pubmed/35888775 http://dx.doi.org/10.3390/metabo12070651 |
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author | Detraux, Damien Renard, Patricia |
author_facet | Detraux, Damien Renard, Patricia |
author_sort | Detraux, Damien |
collection | PubMed |
description | Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several intermediate states have been reported, as well as a small subpopulation of cells that have reacquired features of the 2C-embryo (2C-like cells) in naïve mouse ESC culture. Altogether, these represent a continuum of distinct pluripotency stages, characterized by metabolic transitions, for which we propose a new role for a long-known metabolite: succinate. Mostly seen as the metabolite of the TCA, succinate is also at the crossroad of several mitochondrial biochemical pathways. Its role also extends far beyond the mitochondrion, as it can be secreted, modify proteins by lysine succinylation and inhibit the activity of alpha-ketoglutarate-dependent dioxygenases, such as prolyl hydroxylase (PHDs) or histone and DNA demethylases. When released in the extracellular compartment, succinate can trigger several key transduction pathways after binding to SUCNR1, a G-Protein Coupled Receptor. In this review, we highlight the different intra- and extracellular roles that succinate might play in the fields of early pluripotency and embryo development. |
format | Online Article Text |
id | pubmed-9325148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93251482022-07-27 Succinate as a New Actor in Pluripotency and Early Development? Detraux, Damien Renard, Patricia Metabolites Review Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several intermediate states have been reported, as well as a small subpopulation of cells that have reacquired features of the 2C-embryo (2C-like cells) in naïve mouse ESC culture. Altogether, these represent a continuum of distinct pluripotency stages, characterized by metabolic transitions, for which we propose a new role for a long-known metabolite: succinate. Mostly seen as the metabolite of the TCA, succinate is also at the crossroad of several mitochondrial biochemical pathways. Its role also extends far beyond the mitochondrion, as it can be secreted, modify proteins by lysine succinylation and inhibit the activity of alpha-ketoglutarate-dependent dioxygenases, such as prolyl hydroxylase (PHDs) or histone and DNA demethylases. When released in the extracellular compartment, succinate can trigger several key transduction pathways after binding to SUCNR1, a G-Protein Coupled Receptor. In this review, we highlight the different intra- and extracellular roles that succinate might play in the fields of early pluripotency and embryo development. MDPI 2022-07-15 /pmc/articles/PMC9325148/ /pubmed/35888775 http://dx.doi.org/10.3390/metabo12070651 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Detraux, Damien Renard, Patricia Succinate as a New Actor in Pluripotency and Early Development? |
title | Succinate as a New Actor in Pluripotency and Early Development? |
title_full | Succinate as a New Actor in Pluripotency and Early Development? |
title_fullStr | Succinate as a New Actor in Pluripotency and Early Development? |
title_full_unstemmed | Succinate as a New Actor in Pluripotency and Early Development? |
title_short | Succinate as a New Actor in Pluripotency and Early Development? |
title_sort | succinate as a new actor in pluripotency and early development? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325148/ https://www.ncbi.nlm.nih.gov/pubmed/35888775 http://dx.doi.org/10.3390/metabo12070651 |
work_keys_str_mv | AT detrauxdamien succinateasanewactorinpluripotencyandearlydevelopment AT renardpatricia succinateasanewactorinpluripotencyandearlydevelopment |