Genome-wide identification of target genes for the transcription factor Sox9 in early postnatal NG2 glia.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA910518 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22654329_1.fastq.gz | Fastqsanger.gz | |||
| SRR22654329_2.fastq.gz | Fastqsanger.gz | |||
| SRR22654331_1.fastq.gz | Fastqsanger.gz | |||
| SRR22654331_2.fastq.gz | Fastqsanger.gz | |||
| SRR22654333_1.fastq.gz | Fastqsanger.gz |
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Project description:To identify expression patterns dependent on the transcription factor Sox9 in oligodendroglia in a genome-wide and unbiased approach, we sorted oligodendroglia from wild type and Sox9-overexpressing mice and isolated total RNA which was followed by RNA-Seq studies. Among others we detected substantial changes in the expression of genes associated proliferation, differentiation and myelination of oligodendrocytes.
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2023-09-21 | E-MTAB-11967 | biostudies-arrayexpress
Project description:The transcription factor gene Sox9 plays various roles in development, including differentiation of the skeleton, testes, glia, and heart. Other functions of Sox9 remain enigmatic. Because Sox9 protein regulates expression of target genes, the identification of Sox9 targets should facilitate an understanding of the mechanisms of Sox9 action. To help identify Sox9 targets, we used microarray expression profiling to compare wild-type embryos to mutant embryos lacking activity for sox9a and sox9b, the zebrafish co-orthologs of Sox9. Candidate genes were further evaluated by whole mount in situ hybridization in wild-type and sox9 mutant embryos. Results identified genes expressed in cartilage (col2a1a and col11a2), retina (calb2a, calb2b, crx, neurod, rs1, sox4a and vsx1) and pectoral fin bud (klf2b and EST AI722369) as candidate targets for Sox9. Cartilage is a well-characterized Sox9 target, which validates this strategy, whereas retina represents a novel Sox9 function. Analysis of mutant phenotypes confirmed that Sox9 helps regulate the number of Müller glia and photoreceptor cells and helps organize the neural retina. These roles in eye development were previously unrecognized and reinforce the multiple functions that Sox9 plays in vertebrate development. In each experiment, RNA was isolated from 48h wildtype and sox9a, sox9b double mutant embryos and the gene expression profiles were compared using microarrays. Three biological replicate experiments were performed, and each biological replicate contained a dyeswap.
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Project description:The transcription factor gene Sox9 plays various roles in development, including differentiation of the skeleton, testes, glia, and heart. Other functions of Sox9 remain enigmatic. Because Sox9 protein regulates expression of target genes, the identification of Sox9 targets should facilitate an understanding of the mechanisms of Sox9 action. To help identify Sox9 targets, we used microarray expression profiling to compare wild-type embryos to mutant embryos lacking activity for sox9a and sox9b, the zebrafish co-orthologs of Sox9. Candidate genes were further evaluated by whole mount in situ hybridization in wild-type and sox9 mutant embryos. Results identified genes expressed in cartilage (col2a1a and col11a2), retina (calb2a, calb2b, crx, neurod, rs1, sox4a and vsx1) and pectoral fin bud (klf2b and EST AI722369) as candidate targets for Sox9. Cartilage is a well-characterized Sox9 target, which validates this strategy, whereas retina represents a novel Sox9 function. Analysis of mutant phenotypes confirmed that Sox9 helps regulate the number of Müller glia and photoreceptor cells and helps organize the neural retina. These roles in eye development were previously unrecognized and reinforce the multiple functions that Sox9 plays in vertebrate development.
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Project description:Mouse model with P53f/f;Nf1f/+;Ptenf/+ configuration driven by Nestin-creERT2 and NG2-creERTM induced at 1 month postnatal forms high grade glioma in the brain. Tumors were harvested and total RNA were extracted for gene expression profile.
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Project description:B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, with long-term overall survival rates of 80%. However, B-ALL harboring rearrangements of the MLL gene (also known as KTM2A), hereinafter termed MLLr B-ALL, is frequently seen in infants and is associated with poor 5-year survival (<30%), frequent relapses, and refractoriness to glucocorticoids (GC). GC are an essential part of the treatment backbone for B-ALL and GC resistance is a major clinical predictor of poor outcome. Unraveling the mechanisms of GC resistance in MLLr B-ALL is, therefore, crucial to guide therapeutic strategies that deepen response after induction therapy. Neuron-glial antigen-2 (NG2) expression is a hallmark of MLLr B-ALL and is minimally expressed in healthy hematopoietic cells. We recently reported that NG2 expression is associated with poor prognosis and that anti-NG2 immunotherapy strongly reduces/delays relapse in xenograft models of MLLr B-ALL. However, despite its contribution to MLLr B-ALL pathogenesis and its diagnostic utility, the role of NG2 in MLLr-mediated leukemogenesis/chemoresistance remains elusive. We show here that NG2 is an epigenetically regulated direct target gene of the leukemic MLL-AF4 fusion protein. NG2 negatively regulates the expression of the GC receptor NR3C1, conferring GC chemoresistance to MLLr B-ALL cells in vitro and in vivo. Mechanistically, NG2 interacts with FLT3 to render ligand-independent activation of FLT3 signaling (a hallmark of MLLr B-ALL) and downregulation of NR3C1 via AP-1-mediated transrepression. Collectively, our study elucidates the role of NG2 in GC resistance in MLLr B-ALL through a FLT3/AP-1-mediated downregulation of NR3C1, providing novel therapeutic avenues for MLLr B-ALL.
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