Oct4 redox sensitivity potentiates reprogramming and differentiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1007695 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25721634_1.fastq.gz | Fastqsanger.gz | |||
| SRR25721634_2.fastq.gz | Fastqsanger.gz | |||
| SRR25721635_1.fastq.gz | Fastqsanger.gz | |||
| SRR25721635_2.fastq.gz | Fastqsanger.gz | |||
| SRR25721636_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:The transcription factor Oct4/Pou5f1 is a key component of the regulatory circuitry governing pluripotency. Oct4 is also widely used to generate induced pluripotent stem cells (iPSCs) from somatic cells. These observations provide compelling rationale to understand Oct4’s functions. Here we used domain swapping and mutagenesis to compare Oct4’s reprogramming activity with the paralog Oct1/Pou2f1, identifying a redox-sensitive DNA binding domain cysteine residue (Cys48) as a key determinant of both reprogramming and differentiation. In combination with the Oct4 N-terminus, mutating Oct1’s serine at this position to cysteine is sufficient to confer strong reprogramming activity. Conversely, Oct4C48S strongly reduces reprogramming potential. Oct4C48S renders the protein insensitive to oxidative inhibition of DNA binding. The same mutation prevents oxidation-mediated protein ubiquitylation. An engineered Pou5f1C48S point mutation has little effect on undifferentiated cells embryonic stem cells (ESCs), but upon retinoic acid (RA)-mediated differentiation causes retention of Oct4 expression, decreased proliferation, and increased apoptosis. Transcriptional profiling reveals that the retention of pluripotency also manifests at the RNA level. Pou5f1C48S ESCs also contribute poorly to adult somatic tissues and form less differentiated teratomas. Collectively, the data support a model in which Oct4 redox sensing is a positive reprogramming determinant during one or more reprogramming steps, and mediates Oct4 degradation during differentiation.
2024-04-09 | GSE241332 | 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:Forced expression of four transcription factors Oct4,Sox2, Klf4 and Myc (OSKM) induces somatic cell reprogramming towards pluripotency. Major efforts have been made to characterize the molecular events involved in this process. Yet, it remains elusive how gene expression change, epigenetic landscape remodelling and cell fate conversion are triggered by expression of these Yamanaka factors.To address this gap,we utilized a secondary inducible reprogramming system and performed genome-wide profilings of Oct4 binding, histone modification(H3K4me3/H3K27me3/H3K4me1/H3K27ac), and gene expression analysis during this process. Through integrative analysis, we revealed stage-specific Oct4 binding and enhancer signatures in consistence with gene expression changes,in which the initial regression of somatic program is followed by the gradual acquisition of pluripotent program. Oct4 preferatially binds to H3K4me1 marked enhancer regions and Oct4 binding is positively correlated with active mark H3K27ac. Moreover,we observed significant enhancer activation of epigenetic related genes, especially acetylation associated genes, prior to pluripotency network activation, suggesting a pivotal role of epigenetic remodelling in the process of pluripotency acquisition and maintenance. We used ChIP-seq to explore the global changes of Oct4 binding profiling during OSKM-mediated somatic cell reprogramming. The exogenous Oct4 was tagged with 3XFlag, thus we used anti-flag antibody to monitor exogenous Oct4 changes; anti-Oct4 antibody which recognizes both endogenous and exogenous Oct4 was used to monitor total Oct4 changes during iPSC induction. In addition, we also examined genome-wide H3K4me1/H3K27ac/H3K4me3/H3K27me3/RNAPII profiling during 3Flag-OSKM 2' reprogramming.
2015-12-31 | E-GEOD-67520 | biostudies-arrayexpress
Project description:Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation. Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.
2025-06-19 | GSE286894 | GEO
Project description:Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation. Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.
2025-06-20 | GSE287206 | GEO
Project description:Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation. Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.
2025-06-20 | GSE286895 | GEO
Project description:Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation. Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.
2025-06-19 | GSE287494 | GEO
Project description:Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation. Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.
2025-07-23 | GSE287493 | GEO
Project description:Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation. Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.
2025-06-19 | GSE287492 | GEO
Project description:Heterochromatin lossening by Oct4 in somatic cell reprogramming
| PRJNA532597 | ENA