Base editing in bovine embryos reveals a species-specific role of SOX2 in regulation of pluripotency
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA782550 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17000764_1.fastq.gz | Fastqsanger.gz | |||
| SRR17000764_2.fastq.gz | Fastqsanger.gz | |||
| SRR17000765_1.fastq.gz | Fastqsanger.gz | |||
| SRR17000765_2.fastq.gz | Fastqsanger.gz | |||
| SRR17000766_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Proper lineage specification is extremely important for the embryo's implantation and development. Numerous findings of lineage specification emerged in the mouse embryo but remain unclear in the bovine embryo due to the limited techniques. Here, our study is the first to demonstrate that the single base editor (ABE7.10 and BE3) can be applied to bovine embryos for base conversion, which contributes us to further exploring the lineage specification of the bovine embryo. We further show SOX2 is not necessary for blastocyst formation but is required for ICM maintenance in bovine early embryo development. The underlying mechanism may be that SOX2 promoted the differentiation of ICM by maintaining the expression levels of OCT4 and NANOG. Meanwhile, the disappearance of SOX2 in TE of bovine late blastocyst depended on the expression of CDX2.
2022-03-22 | GSE189318 | GEO
Project 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.
| S-EPMC9286228 | biostudies-literature
Project description:Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed pluripotency regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding from embryonic day 3.5 (E3.5) to E7.5 in the mouse. In E3.5 inner cell mass (ICM), SOX2 regulates the ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, SOX2 occupies preaccessible enhancers in part opened by early-stage expressing TFs TFAP2C and NR5A2. SOX2 then redistributes when cells adopt naive and formative pluripotency by opening enhancers or poising them for further rapid activation. Hence, multifaceted pioneer TF–enhancer interaction underpins pluripotency progression in embryos, including a state in E3.5 ICM that bridges totipotency and pluripotency.
2023-12-15 | GSE203194 | GEO
Project description:Sox2 is a key transcription factor directing embryonic stem cell (ESC) pluripotency. However, the role of SoxB1 proteins in epiblast stem cell (EpiSC) pluripotency is unknown. Here we compare the transcriptomes of pluripotent cells cultured in different conditions that express different levels of Sox2. While highest Sox2 level in ESCs are enriched for naive pluripotency markers, ESCs and EpiSCs expressing the same Sox2 level were transcriptionally distinct. Thus Sox2 levels do not dictate the distinction between ESC and EpiSC states.
2017-12-19 | GSE99185 | GEO
Project description:During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 directly activate the pluripotency-related genes through the corresponding OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory towards the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.
2024-10-14 | GSE264615 | GEO
Project description:During the first lineage segregation, mammalian embryos generate the inner cell mass (ICM) and trophectoderm (TE). ICM gives rise to the epiblast (EPI) that forms all cell types of the body, an ability referred to as pluripotency. The molecular mechanisms that induce pluripotency in embryos remain incompletely elucidated. Using knockout (KO) mouse models in conjunction with low-input ATAC-seq and RNA-seq, we found that Oct4 and Sox2 gradually come into play in the early ICM, coinciding with the initiation of Sox2 expression. Oct4 and Sox2 directly activate the pluripotency-related genes through the corresponding OCT-SOX enhancers in the early ICM. Furthermore, we observed a substantial reorganization of chromatin landscape and transcriptome from the morula to the early ICM stages, which was partially driven by Oct4 and Sox2, highlighting their pivotal role in promoting the developmental trajectory towards the ICM. Our study provides new insights into the establishment of the pluripotency network in mouse preimplantation embryos.
2024-10-14 | GSE264614 | GEO
Project description:Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos
| PRJNA838983 | ENA
Project description:Genes and signaling pathways involved in pluripotency have been studied extensively in mouse and human pre-implantation embryos and embryonic stem (ES) cells. The unsuccessful attempts to generate ES cell lines from other species including cattle suggests that other genes and pathways are involved in maintaining pluripotency in these species. To investigate which genes are involved in bovine pluripotency, expression profiles were generated from morula, blastocyst, trophectoderm and inner cell mass (ICM) samples using microarray analysis. As MAPK inhibition can increase the NANOG/GATA6 ratio in the inner cell mass, additionally blastocysts were cultured in the presence of a MAPK inhibitor and changes in gene expression in the inner cell mass were analyzed. Between morula and blastocyst 3,774 genes were differentially expressed and the largest differences were found in blastocyst up-regulated genes. Gene ontology (GO) analysis shows lipid metabolic process as the term most enriched with genes expressed at higher levels in blastocysts. Genes with higher expression levels in morulae were enriched in the RNA processing GO term. Of the 497 differentially expressed genes comparing ICM and TE the expression of NANOG, SOX2 and POU5F1 was indeed increased in the ICM confirming their evolutionary preserved role in pluripotency. Several genes implicated to be involved in differentiation or fate determination were also expressed at higher levels in the ICM. Genes expressed at higher levels in the ICM were enriched in the RNA splicing and regulation of gene expression GO term. Although NANOG expression was elevated upon MAPK inhibition, SOX2 and POU5F1 expression showed little increase. Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was affected. The data obtained from the microarray studies provide further insight in gene expression during bovine embryonic development. They show an expression profile in pluripotent cells that indicates a pluripotent but epiblast-like state. These data indicate that MAPK inhibition alone is not sufficient to maintain a pluripotent character in bovine cells.
2015-05-07 | GSE63053 | GEO
Project description:Genes and signaling pathways involved in pluripotency have been studied extensively in mouse and human pre-implantation embryos and embryonic stem (ES) cells. The unsuccessful attempts to generate ES cell lines from other species including cattle suggests that other genes and pathways are involved in maintaining pluripotency in these species. To investigate which genes are involved in bovine pluripotency, expression profiles were generated from morula, blastocyst, trophectoderm and inner cell mass (ICM) samples using microarray analysis. As MAPK inhibition can increase the NANOG/GATA6 ratio in the inner cell mass, additionally blastocysts were cultured in the presence of a MAPK inhibitor and changes in gene expression in the inner cell mass were analyzed. Between morula and blastocyst 3,774 genes were differentially expressed and the largest differences were found in blastocyst up-regulated genes. Gene ontology (GO) analysis shows lipid metabolic process as the term most enriched with genes expressed at higher levels in blastocysts. Genes with higher expression levels in morulae were enriched in the RNA processing GO term. Of the 497 differentially expressed genes comparing ICM and TE the expression of NANOG, SOX2 and POU5F1 was indeed increased in the ICM confirming their evolutionary preserved role in pluripotency. Several genes implicated to be involved in differentiation or fate determination were also expressed at higher levels in the ICM. Genes expressed at higher levels in the ICM were enriched in the RNA splicing and regulation of gene expression GO term. Although NANOG expression was elevated upon MAPK inhibition, SOX2 and POU5F1 expression showed little increase. Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was affected. The data obtained from the microarray studies provide further insight in gene expression during bovine embryonic development. They show an expression profile in pluripotent cells that indicates a pluripotent but epiblast-like state. These data indicate that MAPK inhibition alone is not sufficient to maintain a pluripotent character in bovine cells.
2015-05-07 | GSE63050 | GEO
Project description:Genes and signaling pathways involved in pluripotency have been studied extensively in mouse and human pre-implantation embryos and embryonic stem (ES) cells. The unsuccessful attempts to generate ES cell lines from other species including cattle suggests that other genes and pathways are involved in maintaining pluripotency in these species. To investigate which genes are involved in bovine pluripotency, expression profiles were generated from morula, blastocyst, trophectoderm and inner cell mass (ICM) samples using microarray analysis. As MAPK inhibition can increase the NANOG/GATA6 ratio in the inner cell mass, additionally blastocysts were cultured in the presence of a MAPK inhibitor and changes in gene expression in the inner cell mass were analyzed. Between morula and blastocyst 3,774 genes were differentially expressed and the largest differences were found in blastocyst up-regulated genes. Gene ontology (GO) analysis shows lipid metabolic process as the term most enriched with genes expressed at higher levels in blastocysts. Genes with higher expression levels in morulae were enriched in the RNA processing GO term. Of the 497 differentially expressed genes comparing ICM and TE the expression of NANOG, SOX2 and POU5F1 was indeed increased in the ICM confirming their evolutionary preserved role in pluripotency. Several genes implicated to be involved in differentiation or fate determination were also expressed at higher levels in the ICM. Genes expressed at higher levels in the ICM were enriched in the RNA splicing and regulation of gene expression GO term. Although NANOG expression was elevated upon MAPK inhibition, SOX2 and POU5F1 expression showed little increase. Expression of other genes in the MAPK pathway including DUSP4 and SPRY4, or influenced by MAPK inhibition such as IFNT, was affected. The data obtained from the microarray studies provide further insight in gene expression during bovine embryonic development. They show an expression profile in pluripotent cells that indicates a pluripotent but epiblast-like state. These data indicate that MAPK inhibition alone is not sufficient to maintain a pluripotent character in bovine cells. Microarrays used were bovine whole genome gene expression microarrays V2 (Agilent Technologies) representing 43,653 Bos taurus 60-mer oligos in a 4x44K layout. RNA samples from morula, blastocyst and dissected inner cell mass (ICM) and trophectoderm (TE) were compared in a common reference experiment design using 8 dual channel microarrays with each sample hybridized against an identical sample consisting of a pool of blastocysts total RNA. Within each group of two microarrays for each stage/tissue type, sample versus common reference hybridizations were performed in balanced dye-swap.
2015-05-07 | E-GEOD-63050 | biostudies-arrayexpress