An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions.
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ABSTRACT:
PROVIDER: PRJNA145109 | ENA |
REPOSITORIES: ENA
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Project description:Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodelling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Analyses of coordinated expression changes identified strikingly different epigenetic regulatory patterns of pluripotency and differentiation states. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb
2021-02-25 | GSE33191 | GEO
Project description:Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodelling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Analyses of coordinated expression changes identified strikingly different epigenetic regulatory patterns of pluripotency and differentiation states. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb
2021-02-25 | GSE31791 | GEO
Project description:Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodelling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Analyses of coordinated expression changes identified strikingly different epigenetic regulatory patterns of pluripotency and differentiation states. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb
2021-02-25 | GSE31640 | GEO
Project description:Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory "dimensions" coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors, plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb module.
| S-EPMC8017264 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-02-25 | GSE31842 | GEO
Project description:To investigate the molecular mechanisms underlying the reprogramming of epiblast stem cells (EpiSCs) into embryonic stem cells (ESCs) induced by Esrrb, we performed ChIP-seq analysis of Esrrb, Nanog, Oct4, and Sox2 in Tet-on Esrrb EpiSCs after treatment with doxycycline (Dox).
2018-06-01 | E-MTAB-5342 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE34904: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 1) GSE34912: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 2) GSE34918: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 3) GSE34920: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 4) Refer to individual Series
2012-04-05 | E-GEOD-34921 | biostudies-arrayexpress
Project description:Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to be crucial for embryonic stem (ES) self-renewal maintenance and cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these state transitions remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of ES cells that incorporate protein-coding and miRNA genes based on microRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific ES cell miRNA expression program and integrates dynamic changes of feed forward loops contributing to the exit of the pluripotency state upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in stem cells.
2022-03-21 | GSE57371 | GEO
Project description:Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to be crucial for embryonic stem (ES) self-renewal maintenance and cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these state transitions remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of ES cells that incorporate protein-coding and miRNA genes based on microRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific ES cell miRNA expression program and integrates dynamic changes of feed forward loops contributing to the exit of the pluripotency state upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in stem cells.
2022-03-21 | GSE189678 | GEO
Project description:Nucleostemin (NS) gene is known to be expressed in stem cells in general including embryonic stem cells (ESCs). Previous knockdown and knockout studies have demonstrated that NS is important for the preservation of their self-renewality and high levels of pluripotent marker gene expression in mouse ESCs. In this study, we demonstrate that the forced expression of Nanog or Esrrb, but not other pluripotency factors, made NS expression dispensable in mouse ESCs. DNA microarray data deposited here underscored the notion that both Nanog and Esrrb could rather faithfully counteract the alteration of gene expression profile caused by NS expression ablation in ESCs. NS tet off ESCs (Stem Cells 27, 1066-1076, 2009) in which NS gene was homozygously disrupted, but NS cDNA was introduced in ROSA26 gene locus together with tetracycline-off system were used as parental ESCs to examine the effect of NS expression ablation in ESCs. In this study, how alteration of gene expression profile change associated with NS expression ablation was modulated by the forced expression of either constitutively active Stat3 (Stat3mut), Nanog or Esrrb. Effect obtained by the exposure to 2i condition (medium containing 2 kinase inhibitors against MEK and GSK3b) was also examined
2015-01-30 | E-GEOD-56797 | biostudies-arrayexpress