Mus musculus strain:129/Ola
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ABSTRACT:
PROVIDER: PRJNA512586 | ENA |
REPOSITORIES: ENA
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Project description:Retinoic acid (RA) induces rapid differentiation of ESCs, partly by activating expression of the transcription factor Hoxa1, which regulates downstream target genes that promote ESCs differentiation. However, mechanisms of RA-induced Hoxa1 expression and ESCs early differentiation remain largely unknown. Here, we identify a distal enhancer interacting with the Hoxa1 locus through a long-range chromatin loop. Enhancer deletion significantly inhibited expression of RA-induced Hoxa1 and endoderm master control genes such as Gata4 and Gata6. Transcriptome analysis revealed that RA-induced early ESCs differentiation was blocked in Hoxa1 enhancer knockout cells, suggesting a requirement for the enhancer. Restoration of Hoxa1 expression partly rescued expression levels of ~40% of genes whose expression changed following enhancer deletion, and ~18% of promoters of those rescued genes were directly bound by Hoxa1. Our data show that a distal enhancer maintains Hoxa1 expression through long-range chromatin loop and that Hoxa1 directly regulates downstream target gene expression and then orchestrates RA-induced early differentiation of ESCs.
2018-12-24 | GSE124306 | GEO
Project description:Zbtb46 regulated gene expression in ex vivo differentiated embryonic stem cells
| PRJNA647349 | ENA
Project description:We report the genome-wide RNA expression levels in pluripotent mESC and as mESC differentiate towards a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. RNA-seq was performed to identify all RNAs expressed in both ESCs and neuronal cells. In total, In total, 14,443 expressed genes were detected, of which 1,834 were up-regulated and 1,477 down-regulated (fold change (FC) > -/+2.0 and p-value < 0.035) during RA-induced neuronal differentiation. The top down-regulated genes included members of the pluripotency core transcriptional network, including Klf4, Sox2, Oct4, Nanog, Suz12, Esrrb, Stat3 and Tcfcp2l1. The top up-regulated genes are important for neuronal differentiation (e.g. Pax3, Irx3, Rest and Foxd3) and reside in the RA-pathway (e.g. various homeobox genes), the retinoic acid receptors and the RA-degradation enzyme Cyp26a1. Examination, identification and comparision of mRNA expression profliles in two cellular states.
2015-05-01 | E-GEOD-65697 | biostudies-arrayexpress
Project description:We report the genome-wide RNA expression levels in pluripotent mESC and as mESC differentiate towards a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. RNA-seq was performed to identify all RNAs expressed in both ESCs and neuronal cells. In total, In total, 14,443 expressed genes were detected, of which 1,834 were up-regulated and 1,477 down-regulated (fold change (FC) > -/+2.0 and p-value < 0.035) during RA-induced neuronal differentiation. The top down-regulated genes included members of the pluripotency core transcriptional network, including Klf4, Sox2, Oct4, Nanog, Suz12, Esrrb, Stat3 and Tcfcp2l1. The top up-regulated genes are important for neuronal differentiation (e.g. Pax3, Irx3, Rest and Foxd3) and reside in the RA-pathway (e.g. various homeobox genes), the retinoic acid receptors and the RA-degradation enzyme Cyp26a1.
2015-05-01 | GSE65697 | GEO
Project description:We report the genome-wide microRNA expression levels in pluripotent mESC and as mESC differentiate towards a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. microRNA-seq was performed to identify all microRNAs expressed in both ESCs and neuronal cells. In total, 534 expressed microRNAs we identified, of which 18 were up-regulated and 6 were down-regulated (fold change (FC) > -/+2.0 and p-value < 0.05) during Retinoic Acid-induced neuronal differentiation. The top up-regulated microRNAs identified were Mir10a, Mir615, Mir217 and Mir219a-2. The top down-regulated microRNAs identifed were Mir211, Mir292, Mir302a and Mir302c.
2015-05-01 | GSE65696 | GEO
Project description:Characterization of retinoic acid-regulated microRNAs
| PRJNA106491 | ENA
Project description:Signaling pathway driven target gene transcriptions are critical for fate determination of embryonic stem cells (ESC), but enhancer architecture-dependent transcriptional regulation remains largely unclear in this process. Here, we described a complex enhancer architecture-dependent multilayered transcriptional regulation that orchestrates retinoic acid (RA) signal-induced early differentiation of ESC. Specifically, we identified Hoxa1 and lncRNA Halr1 as the direct downstream target genes of RA signal. Chromosome conformation capture based screens show that increased enhancer interactions promoted by RA signal are essential for Hoxa1 and Halr1 expressions during early ESC differentiation. Furthermore, we find that HOXA1 promotes Halr1 expression through direct binding to enhancers; conversely, absence of Halr1 RNA enhances interaction between Hoxa1 chromatin and multiple enhancers, but weakens interaction with HoxA cluster internal chromatin, thereby promoting RA signal-induced Hoxa1 overactivation and early differentiation of ESC. These results indicate that Halr1 binds to chromatin not only acts as a brake to orchestrate interaction between enhancers and Hoxa1 chromatin, but also acts as a binder to maintain chromatin interaction within HoxA cluster. In summary, these findings reveal a complex multilayered transcriptional regulation involving the synergistic regulation of enhancer, transcription factor and lncRNA, and that increases our understanding of the intrinsic molecular mechanisms of RA signal-induced ESC differentiation.
2021-04-16 | GSE169058 | GEO
Project description:We report the genome-wide microRNA expression levels in pluripotent mESC and as mESC differentiate towards a neuronal lineage in response to high levels of Retinoic Acid treatment in vitro. microRNA-seq was performed to identify all microRNAs expressed in both ESCs and neuronal cells. In total, 534 expressed microRNAs we identified, of which 18 were up-regulated and 6 were down-regulated (fold change (FC) > -/+2.0 and p-value < 0.05) during Retinoic Acid-induced neuronal differentiation. The top up-regulated microRNAs identified were Mir10a, Mir615, Mir217 and Mir219a-2. The top down-regulated microRNAs identifed were Mir211, Mir292, Mir302a and Mir302c. Examination, identification and comparision of microRNA expression profliles in two cellular states.
2015-05-01 | E-GEOD-65696 | biostudies-arrayexpress
Project description:S6K1 Knockout mice has a lean phenotype and resitant to a High Fat Diet-induced obesity (Um S.H., Nature, 2004). Adipocyte differentiation consists of two step, first, commitment from stem cell to adipocyte progenitors and second, terminal differentiation from adipocyte progenitors to mature adipocyte. We studied S6K1-dependent gene expression regulation in early stage of commitment by employing ES cell(ESC)-Embryoid Bodies(EBs) differentiation model. We established stable ES cell lines infected with either control non-silencing shRNA (shNS) or S6K1 targetting shRNA (shS6K1). Each sample was treated with retinoic acid for 3 days to induce adipogenesis, then gene expression profile was analyzed employing microarrays and up-regulated and down-regulated genes were selected for analysis. Mouse Embryoid Bodies (approximately 1000 EBs per sample) were treated with retinoic acid (1µM) for 3 days then collected for RNA extraction and hybridization on Affimetrix microarray. Two biological replicates were each performed for EBs prepared from either shNS ESCs or shS6K1 ESCs.
2010-05-14 | E-GEOD-20349 | biostudies-arrayexpress