In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 7 ( 2022-7-5), p. e1010307-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010307
DOI:
10.1371/journal.pgen.1010307.g001
DOI:
10.1371/journal.pgen.1010307.g002
DOI:
10.1371/journal.pgen.1010307.g003
DOI:
10.1371/journal.pgen.1010307.g004
DOI:
10.1371/journal.pgen.1010307.g005
DOI:
10.1371/journal.pgen.1010307.g006
DOI:
10.1371/journal.pgen.1010307.t001
DOI:
10.1371/journal.pgen.1010307.t002
DOI:
10.1371/journal.pgen.1010307.s001
DOI:
10.1371/journal.pgen.1010307.s002
DOI:
10.1371/journal.pgen.1010307.s003
DOI:
10.1371/journal.pgen.1010307.s004
DOI:
10.1371/journal.pgen.1010307.s005
DOI:
10.1371/journal.pgen.1010307.s006
DOI:
10.1371/journal.pgen.1010307.s007
DOI:
10.1371/journal.pgen.1010307.s008
DOI:
10.1371/journal.pgen.1010307.s009
DOI:
10.1371/journal.pgen.1010307.s010
DOI:
10.1371/journal.pgen.1010307.s011
DOI:
10.1371/journal.pgen.1010307.s012
DOI:
10.1371/journal.pgen.1010307.s013
DOI:
10.1371/journal.pgen.1010307.s014
DOI:
10.1371/journal.pgen.1010307.r001
DOI:
10.1371/journal.pgen.1010307.r002
DOI:
10.1371/journal.pgen.1010307.r003
DOI:
10.1371/journal.pgen.1010307.r004
DOI:
10.1371/journal.pgen.1010307.r005
DOI:
10.1371/journal.pgen.1010307.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
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