Role of OCT4 as a transcription factor in pluripotent stem cells [ChIP-seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE282454 | GEO | 2025/07/02
REPOSITORIES: GEO
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Project description:Pluripotent stem cells (PSCs), known for their unlimited ability to self-renew and differentiate into all three germ layers, have emerged as a promising cell source for regenerative therapies aimed at treating various diseases and injuries.
2025-07-02 | GSE288961 | GEO
Project description:Pluripotent stem cells (PSCs), known for their unlimited ability to self-renew and differentiate into all three germ layers, have emerged as a promising cell source for regenerative therapies aimed at treating various diseases and injuries. However, the direct application of pluripotent stem cells brings many problems, including malignant teratoma formation and undirected differentiation. Pluripotent stem cell-derived mesenchymal stem cells may solve these problems. At the same time, pluripotent stem cell-derived mesenchymal stem cells can also solve the problems of adult mesenchymal stem cells, such as limited source, donor site trauma and strong heterogeneity. In this study, pluripotent stem cells were used as the starting point for differentiation into mesenchymal stem cells. Bulk RNA-seq was performed on differentiated cells.
2025-07-02 | GSE281140 | GEO
Project description:Naïve and primed pluripotent stem cells (PSCs) and germ cells express the Pou5f1 (Oct4) gene. The Oct4 gene contains two cis-regulatory elements, the distal (DE) and proximal enhancer (PE), which differentially control Oct4 expression in a cell-type- and stage-specific manner. Here, we generated double transgenic mice carrying both Oct4-ΔPE-GFP and Oct4-ΔDE-tdTomato (RFP), enabling us to simultaneously monitor the activity of DE and PE. Oct4 expression is stage-specifically regulated by DE and PE during embryonic and germ cell development. Using this dual reporter system, we successfully cultured pure populations of naïve (GFP+RFP-) and primed (GFP-RFP+) PSCs. We found that GFP+RFP- cells were metastable in serum-containing medium; stable naïve pluripotent cells were observed in medium containing two inhibitors (Meki and GSKi) but lacking serum. Finally, we suggest that the activity of Oct4 DE and PE is regulated by the repressive histone marks H3K9me3 and DNA methylation.
2015-03-19 | GSE67031 | 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:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells
A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation.
This model is described in the article:
In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.
Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R
BMC Genomics, 2009, 10:314
Abstract:
BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.
RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.
CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.
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2005-01-01 | MODEL1305010000 | BioModels
Project description:Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of the four transcription factors (OCT4, SOX2, c-MYC, KLF4). We previously reported that Oct4 alone is sufficient to directly reprogram adult mouse neural stem cells (NSCs) to iPS cells. Here, we report the generation of one-factor (1F) human iPS from human NSCs (1F hNiPS) by ectopic expression of Oct4 alone. 1F hNiPS cells resemble human embryonic stem cells (hESCs) in global gene expression profiles, epigenetic status and pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human NSCs to pluripotency. 1F iPS cell generation will accelerate this field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.
2009-09-23 | GSE15355 | 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 four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem (1F iPS) cells are similar to embryonic stem cells in vitro and in vivo. Not only can these cells be efficiently differentiated into NSCs, cardiomyocytes and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
2009-02-01 | GSE12499 | GEO
Project description:The success of Yamanaka factor reprogramming mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) suggests that some factor(s) must remodel the nuclei from a condensed state to a relaxed state to facilitate factor binding to target genes. We asked how the Yamanaka factor-dependent chromatin opening occurs. We found Oct4, but neither Sox2 nor Klf4, is responsible for the loosening of the condensed state. Oct4 acts as a pioneer factor that facilitates the binding of Klf4 and the expression of epithelial genes in the early stage of reprogramming.
2021-03-09 | GSE129728 | GEO
Project description:The pluripotency factor Oct4 is essential for the maintenance of naïve pluripotent stem cells in vitro and in vivo. However, the specific role of Oct4 in this process remains unknown. Here, we developed a rapid protein-level Oct4 depletion system that demonstrates that the immediate downstream response to loss of Oct4 is reduced expression of key pluripotency factors. Our data show a requirement for Oct4 for the efficient transcription of several key pluripotency factors, and suggest that expression of trophectoderm markers is a subsequent event. Additionally, we find that Nanog is competent to bind to the genome in the absence of Oct4, and this binding is in fact enhanced. Globally, however, active enhancer associated histone mark H3K27ac is depleted. Our work establishes that while Oct4 is required for the maintenance of the naïve transcription factor network, at a normal ESC level it antagonises this network through inhibition of Nanog binding
2021-06-17 | GSE168577 | GEO