Base editing in bovine embryos reveals a species-specific role of SOX2 in regulation of pluripotency

The emergence of the first three lineages during development is orchestrated by a network of transcription factors, which are best characterized in mice. However, the role and regulation of these factors are not completely conserved in other mammals, including human and cattle. Here, we establish a...

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Veröffentlicht in:PLoS genetics 2022-07, Vol.18 (7), p.e1010307-e1010307
Hauptverfasser: Luo, Lei, Shi, Yan, Wang, Huanan, Wang, Zizengchen, Dang, Yanna, Li, Shuang, Wang, Shaohua, Zhang, Kun
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container_issue 7
container_start_page e1010307
container_title PLoS genetics
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creator Luo, Lei
Shi, Yan
Wang, Huanan
Wang, Zizengchen
Dang, Yanna
Li, Shuang
Wang, Shaohua
Zhang, Kun
description The emergence of the first three lineages during development is orchestrated by a network of transcription factors, which are best characterized in mice. However, the role and regulation of these factors are not completely conserved in other mammals, including human and cattle. Here, we establish a gene inactivation system with a robust efficiency by introducing premature codon with cytosine base editors in bovine early embryos. By using this approach, we have determined the functional consequences of three critical lineage-specific genes (SOX2, OCT4 and CDX2) in bovine embryos. In particular, SOX2 knockout results in a failure of the establishment of pluripotency in blastocysts. Indeed, OCT4 level is significantly reduced and NANOG barely detectable. Furthermore, the formation of primitive endoderm is compromised with few SOX17 positive cells. RNA-seq analysis of single blastocysts (day 7.5) reveals dysregulation of 2074 genes, among which 90% are up-regulated in SOX2-null blastocysts. Intriguingly, more than a dozen lineage-specific genes, including OCT4 and NANOG, are down-regulated. Moreover, SOX2 level is sustained in the trophectoderm in absence of CDX2. However, OCT4 knockout does not affect the expression of SOX2. Overall, we propose that SOX2 is indispensable for OCT4 and NANOG expression and CDX2 represses the expression of SOX2 in the trophectoderm in cattle, which are all in sharp contrast with results in mice.
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subjects Biology and Life Sciences
Blastocysts
Cattle
CDX2 protein
Cell development (Biology)
Cytosine
Editors
Efficiency
Embryos
Endoderm
Gene expression
Genes
Genetic aspects
Genetic research
Genomes
Mutation
Observations
Oct-4 protein
Physical Sciences
Pluripotency
Properties
Proteins
Research and Analysis Methods
Transcription factors
Trophectoderm
title Base editing in bovine embryos reveals a species-specific role of SOX2 in regulation of pluripotency
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