Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo

The spatial sorting of RNA transcripts is fundamental for the refinement of gene expression to distinct subcellular regions. Although, in non-mammalian early embryogenesis, differential RNA localisation presages cell fate determination, in mammals it remains unclear. Here, we uncover apical-to-basal...

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Autores principales: Hawdon, Azelle, Geoghegan, Niall D., Mohenska, Monika, Elsenhans, Anja, Ferguson, Charles, Polo, Jose M., Parton, Robert G., Zenker, Jennifer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229589/
https://www.ncbi.nlm.nih.gov/pubmed/37253716
http://dx.doi.org/10.1038/s41467-023-38436-2
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author Hawdon, Azelle
Geoghegan, Niall D.
Mohenska, Monika
Elsenhans, Anja
Ferguson, Charles
Polo, Jose M.
Parton, Robert G.
Zenker, Jennifer
author_facet Hawdon, Azelle
Geoghegan, Niall D.
Mohenska, Monika
Elsenhans, Anja
Ferguson, Charles
Polo, Jose M.
Parton, Robert G.
Zenker, Jennifer
author_sort Hawdon, Azelle
collection PubMed
description The spatial sorting of RNA transcripts is fundamental for the refinement of gene expression to distinct subcellular regions. Although, in non-mammalian early embryogenesis, differential RNA localisation presages cell fate determination, in mammals it remains unclear. Here, we uncover apical-to-basal RNA asymmetries in outer blastomeres of 16-cell stage mouse preimplantation embryos. Basally directed RNA transport is facilitated in a microtubule- and lysosome-mediated manner. Yet, despite an increased accumulation of RNA transcripts in basal regions, higher translation activity occurs at the more dispersed apical RNA foci, demonstrated by spatial heterogeneities in RNA subtypes, RNA-organelle interactions and translation events. During the transition to the 32-cell stage, the biased inheritance of RNA transcripts, coupled with differential translation capacity, regulates cell fate allocation of trophectoderm and cells destined to form the pluripotent inner cell mass. Our study identifies a paradigm for the spatiotemporal regulation of post-transcriptional gene expression governing mammalian preimplantation embryogenesis and cell fate.
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spelling pubmed-102295892023-06-01 Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo Hawdon, Azelle Geoghegan, Niall D. Mohenska, Monika Elsenhans, Anja Ferguson, Charles Polo, Jose M. Parton, Robert G. Zenker, Jennifer Nat Commun Article The spatial sorting of RNA transcripts is fundamental for the refinement of gene expression to distinct subcellular regions. Although, in non-mammalian early embryogenesis, differential RNA localisation presages cell fate determination, in mammals it remains unclear. Here, we uncover apical-to-basal RNA asymmetries in outer blastomeres of 16-cell stage mouse preimplantation embryos. Basally directed RNA transport is facilitated in a microtubule- and lysosome-mediated manner. Yet, despite an increased accumulation of RNA transcripts in basal regions, higher translation activity occurs at the more dispersed apical RNA foci, demonstrated by spatial heterogeneities in RNA subtypes, RNA-organelle interactions and translation events. During the transition to the 32-cell stage, the biased inheritance of RNA transcripts, coupled with differential translation capacity, regulates cell fate allocation of trophectoderm and cells destined to form the pluripotent inner cell mass. Our study identifies a paradigm for the spatiotemporal regulation of post-transcriptional gene expression governing mammalian preimplantation embryogenesis and cell fate. Nature Publishing Group UK 2023-05-30 /pmc/articles/PMC10229589/ /pubmed/37253716 http://dx.doi.org/10.1038/s41467-023-38436-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hawdon, Azelle
Geoghegan, Niall D.
Mohenska, Monika
Elsenhans, Anja
Ferguson, Charles
Polo, Jose M.
Parton, Robert G.
Zenker, Jennifer
Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
title Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
title_full Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
title_fullStr Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
title_full_unstemmed Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
title_short Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
title_sort apicobasal rna asymmetries regulate cell fate in the early mouse embryo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229589/
https://www.ncbi.nlm.nih.gov/pubmed/37253716
http://dx.doi.org/10.1038/s41467-023-38436-2
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