Evolutionary Origin of Vertebrate Oct4/POUV Functions in Supporting Pluripotency
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PROVIDER: PRJNA623368 | ENA |
REPOSITORIES: ENA
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Project description:Evolutionary Origin of Vertebrate Oct4/POUV Functions in Supporting Pluripotency
| PRJNA758957 | ENA
Project description:Pluripotency is the capacity of early embryonic cells to make all the future lineages of the organism, and the existence of a pluripotent population of cells is important to both germ cell function and the pool of progenitor cells that enable vertebrate development to proceed over time through the process of gastrulation. Oct4, a class V POU transcription factor, is required for maintenance of pluripotency in embryonic stem cells (ESCs) and induction of pluripotency via transcription factor reprogramming. Homologues of Oct4 have been identified in other gnathostomes and classified into two different paralogues: POU5F1 and POU5F3. Here we provide evidence that these proteins are probably derived from a single POUV gene through ancient whole genome duplication events. To approach this issue, we compared the functional conservation and divergence of different POUV proteins in their capacity to support naïve pluripotency in mouse ESCs. We found a strong correlation between POU5F1 activity in naïve pluripotency and the regulation of germ cell specification programs. In contrast, POU5F3 exhibited reduced capacity to support naïve ESCs and its activity in ESCs correlated with the expression of genes associated with pre-gastrulation stages, or primed pluripotency. We detected evidence of this functional segregation as early as Sarcopterygian ancestors, based on the activities of coelacanth POUV proteins. Furthermore, we were able to identify earlier POUV homologues in lamprey and shark, indicating that the earliest point at which mammalian-level pluripotency of both POUV paralogues emerged is between the osteichthyan-chondrichthyan split and the gnathostome-cyclostome split.Taken together, our work highlights the evolutionary history of POUV activities across jawed vertebrates, suggesting that evolutionary pressure has facilitated maintenance of both paralogues over long periods of evolutionary history. In species with both paralogues, subfunctionalization of these proteins appears conserved. However, in many branches of vertebrate evolution, one of these paralogues is lost, suggesting a high level of plasticity in function and precarious balance between retaining both proteins and the overall levels of POUV activity in different developmental systems. While the conserved subfunctionalization of POUV activities evolved at some point just before the appearance of tetrapods, the additional divergent activities of this protein family appear to have evolved independently in each vertebrate lineage after gnathostome radiation.
2021-12-31 | GSE183049 | GEO
Project description:Pluripotency is the capacity of early embryonic cells to make all the future lineages of the organism, and the existence of a pluripotent population of cells is important to both germ cell function and the pool of progenitor cells that enable vertebrate development to proceed over time through the process of gastrulation. Oct4, a class V POU transcription factor, is required for maintenance of pluripotency in embryonic stem cells (ESCs) and induction of pluripotency via transcription factor reprogramming. Homologues of Oct4 have been identified in other gnathostomes and classified into two different paralogues: POU5F1 and POU5F3. Here we provide evidence that these proteins are probably derived from a single POUV gene through ancient whole genome duplication events. To approach this issue, we compared the functional conservation and divergence of different POUV proteins in their capacity to support naïve pluripotency in mouse ESCs. We found a strong correlation between POU5F1 activity in naïve pluripotency and the regulation of germ cell specification programs. In contrast, POU5F3 exhibited reduced capacity to support naïve ESCs and its activity in ESCs correlated with the expression of genes associated with pre-gastrulation stages, or primed pluripotency. We detected evidence of this functional segregation as early as Sarcopterygian ancestors, based on the activities of coelacanth POUV proteins. Furthermore, we were able to identify earlier POUV homologues in lamprey and shark, indicating that the earliest point at which mammalian-level pluripotency of both POUV paralogues emerged is between the osteichthyan-chondrichthyan split and the gnathostome-cyclostome split.Taken together, our work highlights the evolutionary history of POUV activities across jawed vertebrates, suggesting that evolutionary pressure has facilitated maintenance of both paralogues over long periods of evolutionary history. In species with both paralogues, subfunctionalization of these proteins appears conserved. However, in many branches of vertebrate evolution, one of these paralogues is lost, suggesting a high level of plasticity in function and precarious balance between retaining both proteins and the overall levels of POUV activity in different developmental systems. While the conserved subfunctionalization of POUV activities evolved at some point just before the appearance of tetrapods, the additional divergent activities of this protein family appear to have evolved independently in each vertebrate lineage after gnathostome radiation.
2020-12-31 | GSE148167 | GEO
Project description:The evolutionary origins of the gene network underlying cellular pluripotency, a central theme in developmental biology, have yet to be elucidated. In mammals, Oct4 is a factor crucial in the reprogramming of differentiated cells into induced pluripotent stem cells. The Oct4 and Pou2 genes evolved from a POU class V gene ancestor, but it is unknown whether pluripotency induced by Oct4 gene activity is a feature specific to mammals or was already present in ancestral vertebrates. Here we report that different vertebrate Pou2 and Oct4 homologues can induce pluripotency in mouse and human fibroblasts and that the inability of zebrafish Pou2 to establish pluripotency is not representative of all Pou2 genes, as medaka Pou2 and axolotl Pou2 are able to reprogram somatic cells into pluripotent cells. Therefore, our results indicate that induction of pluripotency is not a feature specific to mammals, but existed in the Oct4/Pou2 common ancestral vertebrate. 16 samples were analyzed Notation: O: stands for OCT4 reprogramming factor from human; o: stands for Oct4 reprogramming factor from Axolotl S: stands for SOX2 reprogramming factor from human; s: stands for SOX2 reprogramming factor from Axolotl K: stands for KLF4 reprogramming factor from human
2014-03-23 | E-GEOD-21302 | biostudies-arrayexpress
Project description:The evolutionary origins of the gene network underlying cellular pluripotency, a central theme in developmental biology, have yet to be elucidated. In mammals, Oct4 is a factor crucial in the reprogramming of differentiated cells into induced pluripotent stem cells. The Oct4 and Pou2 genes evolved from a POU class V gene ancestor, but it is unknown whether pluripotency induced by Oct4 gene activity is a feature specific to mammals or was already present in ancestral vertebrates. Here we report that different vertebrate Pou2 and Oct4 homologues can induce pluripotency in mouse and human fibroblasts and that the inability of zebrafish Pou2 to establish pluripotency is not representative of all Pou2 genes, as medaka Pou2 and axolotl Pou2 are able to reprogram somatic cells into pluripotent cells. Therefore, our results indicate that induction of pluripotency is not a feature specific to mammals, but existed in the Oct4/Pou2 common ancestral vertebrate.
2014-03-23 | GSE21302 | GEO
Project description:Oct4 is considered a master transcription factor for pluripotent cell self-renewal and embryo development. It primarily collaborates with other transcriptional factors or coregulators to maintain pluripotency. However, it is still unclear how Oct4 interacts with its partners. Here, we show that the Oct4 linker interface mediates competing and balanced Oct4 protein interactions which are crucial for maintaining pluripotency. Linker mutant ESCs maintain the key pluripotency genes expression, but show decreased expression of self-renewal genes and increased expression of differentiation genes which result in impaired ESCs self-renewal and early embryonic lethality. Linker mutation dose not affect Oct4 genomic binding and transactivation potential, but breaks the balanced Oct4 interactome. In mutant ESCs, the interaction between Oct4 and Klf5 was decreased, but interactions between Oct4 and Cbx1, Ctr9, Cdc73 were increased which disrupt the epigenetic state of ESCs. Overexpression of Klf5 or knockdown Cbx1, Cdc73 rescue the cellular phenotype of linker mutant ESCs by rebalancing Oct4 interactome indicating that different partners interact with Oct4 competitively. Thus, by showing how Oct4 interacts with different partners, we provide novel molecular insights to explain how Oct4 contributes to the maintenance of pluripotency.
2021-12-10 | PXD017456 | Pride
Project description: Not available
| S-EPMC4892893 | biostudies-literature
Project description:OCT4 is a fundamental component of the molecular circuitry governing pluripotency in vivo and in vitro. To determine how OCT4 establishes and protects the pluripotent lineage in the embryo, we used comparative single cell transcriptomics and quantitative immunofluorescence on control and OCT4 null blastocyst inner cell masses at two developmental stages. Surprisingly, activation of most pluripotency-associated transcription factors in the early mouse embryo occurs independently of OCT4, with the exception of the JAK/STAT signalling machinery. Concurrently, OCT4 null inner cell masses ectopically activate a subset of trophectoderm-associated genes. Inspection of metabolic pathways implicates regulation of rate-limiting glycolytic enzymes by OCT4, consistent with a role in sustaining glycolysis. Furthermore, upregulation of the lysosomal pathway was specifically detected in OCT4 null embryos. This finding implicates a requirement for OCT4 in production of normal trophectoderm. Collectively, our findings uncover regulation of cellular metabolism and biophysical properties as mechanisms by which OCT4 instructs pluripotency.
2021-01-03 | GSE159030 | GEO
Project description:The mechanisms whereby the crucial pluripotency transcription factor Oct4 regulates target gene expression are incompletely understood. Using an assay system based on partially differentiated embryonic stem cells, we show that Oct4 opposes accumulation of local H3K9me2, and subsequent Dnmt3a-mediated DNA methylation. Upon binding DNA, Oct4 recruits the histone lysine demethylase Jmjd1c. ChIP timecourse experiments identify a stepwise Oct4 mechanism involving Jmjd1c recruitment and H3K9me2 demethylation, transient FACT complex recruitment, and nucleosome depletion. Genome-wide and targeted ChIP confirms binding of newly-synthesized Oct4, together with Jmjd1c and FACT, to the Pou5f1 enhancer and a small number of other Oct4 targets, including the Nanog promoter. Histone demethylation is required for both FACT recruitment and H3 depletion. Jmjd1c is required to induce endogenous Oct4 expression and fully reprogram fibroblasts to pluripotency, indicating that the assay system identifies functional Oct4 cofactors. These findings indicate that Oct4 sequentially recruits activities that catalyze histone demethylation and depletion.
2015-01-23 | GSE65192 | GEO
Project description:The mechanisms whereby the crucial pluripotency transcription factor Oct4 regulates target gene expression are incompletely understood. Using an assay system based on partially differentiated embryonic stem cells, we show that Oct4 opposes accumulation of local H3K9me2, and subsequent Dnmt3a-mediated DNA methylation. Upon binding DNA, Oct4 recruits the histone lysine demethylase Jmjd1c. ChIP timecourse experiments identify a stepwise Oct4 mechanism involving Jmjd1c recruitment and H3K9me2 demethylation, transient FACT complex recruitment, and nucleosome depletion. Genome-wide and targeted ChIP confirms binding of newly-synthesized Oct4, together with Jmjd1c and FACT, to the Pou5f1 enhancer and a small number of other Oct4 targets, including the Nanog promoter. Histone demethylation is required for both FACT recruitment and H3 depletion. Jmjd1c is required to induce endogenous Oct4 expression and fully reprogram fibroblasts to pluripotency, indicating that the assay system identifies functional Oct4 cofactors. These findings indicate that Oct4 sequentially recruits activities that catalyze histone demethylation and depletion. Examination of transcription factor occupancy in cells with newly synthesized Oct4.
2015-01-23 | E-GEOD-65192 | biostudies-arrayexpress