Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo

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dc.contributor.authorHawdon, A.
dc.contributor.authorGeoghegan, N.D.
dc.contributor.authorMohenska, M.
dc.contributor.authorElsenhans, A.
dc.contributor.authorFerguson, C.
dc.contributor.authorPolo, J.M.
dc.contributor.authorParton, R.G.
dc.contributor.authorZenker, J.
dc.date.issued2023
dc.description.abstractThe 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.
dc.description.statementofresponsibilityAzelle Hawdon, Niall D. Geoghegan, Monika Mohenska, Anja Elsenhans, Charles Ferguson, Jose M. Polo, Robert G. Parton, Jennifer Zenker
dc.identifier.citationNature Communications, 2023; 14(1):1-18
dc.identifier.doi10.1038/s41467-023-38436-2
dc.identifier.issn2041-1723
dc.identifier.issn2041-1723
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/139787
dc.language.isoen
dc.publisherNature Research (part of Springer Nature)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2002507
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2009409
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2004627
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1140064
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1150083
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1156489
dc.rights© The Author(s) 2023. 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/.
dc.source.urihttps://doi.org/10.1038/s41467-023-38436-2
dc.subjectCell lineage; embryonic stem cells; lysosomes; microtubules; ribosome
dc.subject.meshBlastocyst
dc.subject.meshAnimals
dc.subject.meshMammals
dc.subject.meshMice
dc.subject.meshRNA
dc.subject.meshCell Differentiation
dc.subject.meshGene Expression Regulation, Developmental
dc.subject.meshEmbryonic Development
dc.subject.meshEmbryo, Mammalian
dc.titleApicobasal RNA asymmetries regulate cell fate in the early mouse embryo
dc.typeJournal article
pubs.publication-statusPublished

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