Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo

Abstract 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...

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Main Authors: Azelle Hawdon, Niall D. Geoghegan, Monika Mohenska, Anja Elsenhans, Charles Ferguson, Jose M. Polo, Robert G. Parton, Jennifer Zenker
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-38436-2
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author Azelle Hawdon
Niall D. Geoghegan
Monika Mohenska
Anja Elsenhans
Charles Ferguson
Jose M. Polo
Robert G. Parton
Jennifer Zenker
author_facet Azelle Hawdon
Niall D. Geoghegan
Monika Mohenska
Anja Elsenhans
Charles Ferguson
Jose M. Polo
Robert G. Parton
Jennifer Zenker
author_sort Azelle Hawdon
collection DOAJ
description Abstract 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 doaj.art-3093f793cc1d41fd8f0d24d20c718b392023-06-04T11:33:07ZengNature PortfolioNature Communications2041-17232023-05-0114111810.1038/s41467-023-38436-2Apicobasal RNA asymmetries regulate cell fate in the early mouse embryoAzelle Hawdon0Niall D. Geoghegan1Monika Mohenska2Anja Elsenhans3Charles Ferguson4Jose M. Polo5Robert G. Parton6Jennifer Zenker7Australian Regenerative Medicine Institute, Monash UniversityWalter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of MelbourneDepartment of Anatomy and Developmental Biology, Development and Stem Cells Program, Monash Biomedicine Discovery InstituteDepartment of Biology, University of Duisburg-EssenInstitute for Molecular Bioscience, University of QueenslandAustralian Regenerative Medicine Institute, Monash UniversityInstitute for Molecular Bioscience, University of QueenslandAustralian Regenerative Medicine Institute, Monash UniversityAbstract 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.https://doi.org/10.1038/s41467-023-38436-2
spellingShingle Azelle Hawdon
Niall D. Geoghegan
Monika Mohenska
Anja Elsenhans
Charles Ferguson
Jose M. Polo
Robert G. Parton
Jennifer Zenker
Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
Nature Communications
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
url https://doi.org/10.1038/s41467-023-38436-2
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