Genome editing reveals a role for OCT4 in human embryogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-10

AUTHORS

Norah M. E. Fogarty, Afshan McCarthy, Kirsten E. Snijders, Benjamin E. Powell, Nada Kubikova, Paul Blakeley, Rebecca Lea, Kay Elder, Sissy E. Wamaitha, Daesik Kim, Valdone Maciulyte, Jens Kleinjung, Jin-Soo Kim, Dagan Wells, Ludovic Vallier, Alessandro Bertero, James M. A. Turner, Kathy K. Niakan

ABSTRACT

Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR-Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR-Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development. More... »

PAGES

67

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature24033

    DOI

    http://dx.doi.org/10.1038/nature24033

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1091861773

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28953884


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    448 Department of Chemistry, Seoul National University, Seoul 151-747, South Korea
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    453 https://www.grid.ac/institutes/grid.451388.3 schema:alternateName The Francis Crick Institute
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