Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA278753 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Naïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even in the absence of other differentiation cues, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a large subset of primed pluripotency-associated genes and redirect Oct4 to thousands of previously inaccessible sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to function as pioneers is highly context-dependent transcription profile of ESCs and EpiLCs to analzye changes during differentiation and the effect of Otx2 loss and overexpression on the differentiation properties
2014-06-05 | E-GEOD-56096 | biostudies-arrayexpress
Project description:The role of mitochondria dynamics and its molecular regulators remains largely unknown during naïve-to-primed pluripotent cell interconversion. Here we report that mitochondrial MTCH2 is a regulator of mitochondrial fusion, essential for the naïve-to-primed interconversion of murine embryonic stem cells (ESCs). During this interconversion, wild-type ESCs elongate their mitochondria and slightly alter their glutamine utilization. In contrast, MTCH2-/- ESCs fail to elongate their mitochondria and to alter their metabolism, maintaining high levels of histone acetylation and expression of naïve pluripotency markers. Importantly, enforced mitochondria elongation by the pro-fusion protein Mitofusin (MFN) 2 or by a dominant negative form of the pro-fission protein dynamin-related protein (DRP) 1 is sufficient to drive the exit from naïve pluripotency of both MTCH2-/- and wild-type ESCs. Taken together, our data indicate that mitochondria elongation, governed by MTCH2, plays a critical role and constitutes an early driving force in the naïve-to-primed pluripotency interconversion of murine ESCs.
2018-11-10 | GSE122067 | GEO
Project description:Although cell therapies require large numbers of quality-controlled hPSCs, existing technologies are limited in their ability to efficiently grow and scale stem cells. We report here that cell-state conversion from primed-to-naïve pluripotency enhances the biomanufacturing of hPSCs. Naïve hPSCs exhibit superior growth kinetics and aggregate formation characteristics in stirred suspension bioreactors compared to their primed counterparts. Moreover, we demonstrate the role of the bioreactor mechanical environment in the maintenance of naïve pluripotency, through transcriptomic enrichment of mechano-sensing signaling for cells in the bioreactor along with a decrease in expression of lineage-specific and primed pluripotency hallmarks. Bioreactor-cultured, naïve hPSCs express epigenetic regulatory transcripts associated with naïve pluripotency, and display hallmarks of X-chromosome reactivation. They exhibit robust production of naïve pluripotency metabolites and display reduced expression of primed pluripotency cell surface markers. We also show that these cells retain the ability to undergo targeted differentiation into beating cardiomyocytes, hepatocytes, and neural rosettes. They additionally display faster kinetics of teratoma formation compared to their primed counterparts. Naïve bioreactor hPSCs also retain structurally stable chromosomes. Our research corroborates that converting hPSCs to the naïve state enhances hPSC manufacturing and indicates a potentially important role for the bioreactor’s mechanical environment in maintaining naïve pluripotency.
2020-05-08 | ST001377 | MetabolomicsWorkbench
Project description:Naïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even in the absence of other differentiation cues, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a large subset of primed pluripotency-associated genes and redirect Oct4 to thousands of previously inaccessible sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to function as pioneers is highly context-dependent
2014-06-05 | GSE56096 | GEO
Project description:Naïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even in the absence of other differentiation cues, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a large subset of primed pluripotency-associated genes and redirect Oct4 to thousands of previously inaccessible sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to function as pioneers is highly context-dependent
2014-06-05 | GSE56098 | GEO
Project description:The enhancer landscape is dramatically restructured as naïve preimplantation epiblasts transition to the post-implantation state of primed pluripotency. A key factor in this process is Otx2, which is upregulated during the early stages of this transition and ultimately recruits Oct4 to a different set of enhancers. In this study we discover that the acetylation status of Oct4 regulates the induction of the primed pluripotency gene network. Maintenance of the naïve state requires Oct4 deacetylation by the NAD-dependent deacetylase, SirT1. The activity of SirT1 is reduced during the naïve to primed transition, thereby increasing the acetylation of Oct4 and promoting its binding to an Otx2 enhancer to induce Otx2 expression. Induction of Otx2 causes the reorganization of acetylated Oct4 and results in the induction of the primed pluripotency gene network. Regulation of Oct4 by SirT1 may link stem cell development to environmental conditions and provide strategies to manipulate epiblast cell state.
2016-09-20 | GSE81494 | GEO
Project description:Naïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even in the absence of other differentiation cues, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a large subset of primed pluripotency-associated genes and redirect Oct4 to thousands of previously inaccessible sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to function as pioneers is highly context-dependent ChIP-seq analysis was performed to map enhancers and associated transcription factors. We used H3K27ac, H3K4me1 and p300 to call enhancers from 2 different pluripotent cell states: ESC and EpiLC. In addition we performed ChIP-seq for Oct4 and Otx2 from these cell states. All these experiments were carried out in replicates, for the EpiLC state the replicates were performed with and without ActivinA. Additionally we carried out ChIPseq for Otx2 and Oct4 in Otx2ko cell lines in which we integrated an inducible Otx2 gene before and after induction with doxycycline.
2014-06-05 | E-GEOD-56098 | biostudies-arrayexpress
Project description:Distinct cell cycle control in naïve and primed mouse pluripotency [RNA-seq]
| PRJNA389945 | ENA
Project description:Distinct cell cycle control in naïve and primed mouse pluripotency [gDNA-seq]
| PRJNA389946 | ENA
Project description:Distinct cell cycle control in naïve and primed mouse pluripotency [ChIP-seq]
| PRJNA389944 | ENA