Project description:The basic helix-loop-helix proteins Olig1 and Olig2 are expressed in high grade, aggressive human glioblastoma multiformes (GBMs). Here we investigated genetic mechanisms regulating Olig1/2 function during gliomagenesis. Although Olig2 function is necessary for early-aggressive tumor formation in a genetically relevant model of classic GBMs with intact p53 function, late-onset gliomas do eventually form. Using an unbiased approach, we identified Id4, encoding a negative HLH protein, as a gene target potently repressed by Olig2 in glioma progenitors. Although Id4 is thought to antagonize proneural genes involved in differentiation, we report a paradoxical role for Id4 in glioma. Genetic deletion of Id4 converts Olig2-/- gliomas to the early-aggressive form, and conversely, overexpression of Id4 inhibits intact Olig2 and prevents even late-onset tumors. Olig1 overexpression is sufficient for gliomagenesis in an Id4-dependent manner. Together, these findings indicate that gliomagenic factors Olig1 and Olig2 are opposed by Id4 function, which acts as tumor suppressor in p53-intact gliomas.
Project description:To investigate the glioma mouse model by knocking out Pten and Trp53 in embryonal Olig2 and Olig1 positive cells in glioma pathogenesis. ATAC-seq
Project description:To investigate the glioma mouse model by knocking out Pten and Trp53 in embryonal Olig2 and Olig1 positive cells in glioma pathogenesis. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for H3K27Ac in PPO1 and PPO2 mouse glioma cell lines and compare the active enhancers with oligodendrocyte progenitor cells.
Project description:To investigate the glioma mouse model by knocking out Pten and Trp53 in embryonal Olig2 and Olig1 positive cells in glioma pathogenesis. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 PPO2, 4 PPO1 and 2 OPN cell lines.
Project description:Astrocyte maturation is crucial for brain function, yet the mechanisms regulating this process remain poorly understood. In this study, we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation. We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating BMP7 expression. Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology, including reduced process complexity, and an immature gene expression profile. Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state, marked by elevated levels of HOPX and GFAP, resembling human astrocytes. Mechanistically, Olig1 and Olig2 bind directly to the Bmp7 enhancer, repressing its expression to promote astrocyte maturation. Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants, confirming the critical role of BMP7 signaling in this process. These findings provide new insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation, with potential implications for understanding glial dysfunction in neurological diseases.
