SOX1OT V1 Acts as a Decoy of HDAC10 to Promote SOX1-dependent hESC Neuronal Differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE186233 | GEO | 2021/10/26
REPOSITORIES: GEO
Similar Datasets
Project description:SOX1OT V1 Acts as a Decoy of HDAC10 to Promote SOX1-dependent hESC Neuronal Differentiation
| PRJNA773048 | ENA
Project description:Long noncoding RNAs (lncRNAs) are abundantly expressed in the nervous system, but their regulatory roles in neuronal differentiation are poorly understood. Using a human embryonic stem cell (hESC)-based 2D neural differentiation approach and a 3D cerebral organoid system, we show that SOX1-OT variant 1 (SOX1-OT V1), a SOX1 overlapping noncoding RNA, plays essential roles in both dorsal cortical neuron differentiation and ventral GABAergic neuron differentiation by facilitating SOX1 expression. SOX1-OT V1 physically interacts with HDAC10 through its 5' region, acts as a decoy to block HDAC10 binding to the SOX1 promoter, and thus maintains histone acetylation levels at the SOX1 promoter. SOX1 in turn activates ASCL1 expression and promotes neuronal differentiation. Taken together, we identify a SOX1-OT V1/HDAC10-SOX1-ASCL1 axis, which promotes neurogenesis, highlighting a role for lncRNAs in hESC neuronal differentiation.
| S-EPMC8811645 | biostudies-literature
Project description:To understand how SOX1's binding profile in neural progenitor with different regional identities, we differentiated hESC into neural progenitors with rostral and caudal identies throught modulating Wnt signaling pathway. We collected cells at neural differentiation day 4 and 8, and performed SOX1 ChIP-seq to investigate SOX1's genome wide binding profiles. These results provide important information for the mechanism underlying SOX1's functions in early regionalization.
2020-08-26 | GSE138215 | GEO
Project description:During human embryogenesis, primitive neural cells start to be generated at the time of gastrulation and gradually acquire regional identities, which is a process called neural patterning. But how intrinsic factors respond to exogenous patterning signals remains poorly understood. Human Embryonic Stem Cells (hESCs) provide a great model to recapitulate this process. Through exogenous manipulation of canonical WNT signaling activation during neural differentiation, dose-dependent specification of regionally defined neural progenitors ranging from the telencephalic forebrain to posterior hindbrain could be rapidly and efficiently induced. Unexpectedly, we find that SOX1, generally referred as a pan-neural gene, displays a regional specific distribution in the human neural patterning process. To investigate the expression and function of SOX1 efficiently, we have generated the SOX1-EGFP reporter and SOX1-knockout (KO) hESC lines using the CRISPR/Cas9 system. SOX1 is initially expressed across the mes–met border and peaked in the metencephalon region at the early regional specification stage. Its depletion leads to the posterior shift of the mes–met border. Therefore, SOX1 is required to define the border at a correct region. In-depth analysis of SOX1 ChIP-sequencing and transcriptome data will provide more insights into how SOX1 determines the mes-met border formation and identify the downstream targets of SOX1. This study identifies SOX1 as one of the intrinsic factors key for the prepattern establishment in the developing central nervous system, particularly for defining the isthmus position.
2020-08-26 | GSE138217 | GEO
Project description:Long noncoding RNAs (lncRNAs) are abundantly expressed in the nervous system, but their regulatory roles in neuronal differentiation are poorly understood. Using a human embryonic stem cell (hESC)-based 2D neural differentiation approach and a 3D cerebral organoid system, we show that SOX1-OT variant 1 (SOX1-OT V1), a SOX1 overlapping noncoding RNA, plays essential roles in both dorsal cortical neuron and ventral GABAergic neuron differentiation by facilitating SOX1 expression. SOX1-OT V1 physically interacts with HDAC10 through its 5' region, acts as a decoy to block HDAC10 binding to the SOX1 promoter, and thus maintains histone acetylation levels at the SOX1 promoter. SOX1 in turn activates ASCL1 expression and promotes neuronal differentiation. Taken together, we identify a SOX1-OT V1/HDAC10-SOX1-ASCL1 axis, which promotes neurogenesis, highlighting a role for lncRNAs in hESC neuronal differentiation.
| S-SCDT-EMBOR-2021-53015V1 | biostudies-other
Project description:The dentate gyrus of the hippocampus continues generating new neurons throughout life. These nerve cells originate from radial astrocytes within the subgranular zone (SGZ). We find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1 driven reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population. We used microarrays to evaluate the molecular constitution of neural stem cells with aging.
2012-08-09 | GSE39992 | GEO
Project description:Region-specific neural progenitor cells (NPCs) can be generated from human embryonic stem cells (hESCs) through modulating signaling pathways. However, how intrinsic transcriptional factors contribute to the neural regionalization are not well characterized. Here, we generate region-specific NPCs from hESCs and find that SOX1 is highly expressed in NPCs with the rostral hindbrain identity. Moreover, we find that OTX2 inhibits SOX1 expression, displaying exclusive expression between the two factors. Furthermore, SOX1 knockout (KO) leads to up-regulation of midbrain genes and down-regulation of rostral hindbrain genes, indicating that SOX1 is necessary for specification of rostral hindbrain NPCs. Our SOX1 ChIP-sequencing analysis reveals that SOX1 binds to the distal region of GBX2 to activate its expression. Overexpression of GBX2 largely abrogates SOX1-KO induced aberrant gene expression. Taken together, this study uncovers previously unappreciated role of SOX1 in early neural regionalization and provides new information for the precise control of the OTX2/GBX2 interface.
2020-08-26 | GSE138218 | GEO
Project description:The dentate gyrus of the hippocampus continues generating new neurons throughout life. These nerve cells originate from radial astrocytes within the subgranular zone (SGZ). We find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1 driven reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population. We used microarrays to evaluate the molecular constitution of neural stem cells with aging. Hippocampi were isolated from Sox1-GFP mice at 5-7 months (n=3) or 1 year 9 months (n=4) using a Leica dissecting scope. Cells were immediately dissociated using papain (Worthington Biochemical Corporation. Lakewood, NJ, USA) and sorted for the GFP high or GFP negative population using a FACSAria Flow Cytometer (BD Biosciences, San Diego, CA, USA). RNA was harvested using the Arcturus PicoPure RNA isolation kit (Life Technologies Corp, Carlsbad, CA, USA) and the quality and quantity of each sample was checked using Agilent BioAnalyzer (Santa Clara, CA, USA) and Nanodrop spectrophotometer (Wilmington, DE, USA). Samples were amplified using the NuGEN FFPE kit (San Carlos, CA, USA) and cDNA was prepared using an oligo(dT)-T7 RNA polymerase primer before biotinylation by in vitro transcription, partial hydrolysis and final hybridization to the Affymetrix (Santa Clara, CA, USA) GeneChip Mouse Gene 1.0 ST Array (Gladstone Genomics Core). Arrays were normalized using Robust Multichip Average (RMA) and the latest probe map to MM9 RefSeq genes (Irizarry et al., 2003; Dai et al., 2005). To detect potential outlier arrays, the distributions of fold changes between all possible pairs within each group were analyzed. One sample from a young mouse was found to have a skewed distribution when compared to other biological replicate samples and was removed from further analysis. The statistical package R was used to perform average linkage hierarchical clustering of the remaining samples. Significance Analysis of Microarrays (SAM) was performed to determine significant differentially expressed genes between the old and young mice with a False Discovery Rate cutoff of 5% (Tusher et al., 2001).
2012-08-08 | E-GEOD-39992 | biostudies-arrayexpress
Project description:Competitive hybridization of V1 variant of genome sequenced C. jejuni strain 11168 versus V1 variant in which flhA gene has been disrupted. Keywords: repeat sample
2004-03-03 | GSE530 | GEO
Project description:Competive hybridization of V1 variant of genome sequenced C. jejuni strain 11168 versus V1 variant in which fliA gene encoding sigma 28 has been disrupted Keywords: repeat sample
2004-03-03 | GSE521 | GEO