Project description:High expression of the ETS family transcription factor ERG is associated with poor clinical outcome in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL). In murine models, high ERG expression induces both T-ALL and AML. However, no study to date has defined the effect of high ERG expression on primary human hematopoietic cells. In the present study, human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG AML. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. Integration of the genome-wide expression data with other data sets revealed that high ERG drives an expression signature that shares features of normal hematopoietic stem cells, high ERG AMLs, early T-cell precursor-ALLs and leukemic stem cell signatures associated with poor clinical outcome. Functional assays linked this gene expression profile to enhanced progenitor cell expansion. These results support a model whereby a stem cell gene expression network driven by high ERG in human cells enhances the expansion of the progenitor pool, providing opportunity for the acquisition and propagation of mutations and the development of leukemia.
Project description:This dataset contains rawRNA-seq data from HFL-1 Cells Overexpressed GFP, GFP-ERG or GFP-ERG-ΔIDR13. The experiment aims to explore the downstream genes of ERG and its phase separation-deficient mutant to uncover the role of ERG's LLPS activity in regulating gene expression in HFL-1 cells, providing insights into the regulatory networks controlled by ERG in cell senescence.
Project description:We provide the functional and epigenomic evidence for ERG binding to super-enhancers in HUVEC and further show that loss of ERG results in inhibition of specific endothelial super-enhancers and associated target genes.
Project description:The goal of this project was to analyze the global gene expression profiles of RWPE1 and VCAP cells following transfection of GFP, GFP-ERG at 48 and 72hrs time points and stable ERG shRNA, scramble shRNA, respectively.
Project description:We provide the functional and epigenomic evidence for ERG binding to super-enhancers in HUVEC and further show that loss of ERG results in inhibition of specific endothelial super-enhancers and associated target genes.
Project description:The goal of this project was to analyze the global gene expression profiles of RWPE1 and VCAP cells following transfection of GFP, GFP-ERG at 48 and 72hrs time points and stable ERG shRNA, scramble shRNA, respectively. RWPE1 cells were transfected with GFP or GFP-ERG. VCAP cells were transfected with ERG lenti-shRNA or scramble shRNA. Transfections were performed in duplicate. Total cellular RNA was isolated with Trizol and quality analysed by the bioanalyser kit.
Project description:Radiotherapy (RT) is a key treatment for prostate cancer (PCa), relying on the ability to induce DNA damage, particularly double-strand breaks (DSBs). The success of RT depends on tumor radiosensitivity and the ability to repair DSBs, making inhibitors of DSB repair enzymes a potential strategy for radiosensitization. However, these inhibitors often lack tumor specificity and can be toxic to normal cells. Thus, tumor-specific radiosensitization strategies are needed for PCa. PCa is frequently associated with chromosomal rearrangements, including the TMPRSS2-ERG translocation, which leads to ERG overexpression (ERG+), present in ~50% of PCa patients. In this study, we show that ERG+ expression shifts DSB repair to the PARP1-dependent end joining (PARP1-EJ) pathway. Western blotting revealed increased expression of PARP1, XRCC1, and LIG3 in ERG+ cells. Notably, PARP inhibition with olaparib increased residual H2AX/53BP1 foci in ERG+ cells after ionizing radiation (IR), rendering cellular radiosensitization by PARPi. Using ex vivo tissue slice (TSC) cultures from 53 tumor tissues of 40 high-risk PCa patients. … Olaparib treatment significantly increased H2AX/53BP1 foci selectively in ERG+ samples, suggesting that ERG expression predicts sensitivity to PARPi as radiosensitizers. Additionally, ERG+ patient-derived organoids showed a significant growth delay when treated with olaparib plus IR, compared to either treatment alone. Interestingly, the radiosensitizing effect of olaparib was also observed in ERG-negative cells within the TSC of ERG+ patients, with residual 53BP1 foci levels comparable to those in ERG+ cells. This was confirmed by medium exchange experiments. In conclusion, ERG overexpression drives a shift in DSB repair to the PARP1-EJ pathway, enhancing radiosensitivity to PARP inhibition. These findings support combining PARP inhibitors with RT for tumor-specific radiosensitization in ERG+ PCa patients.
Project description:We performed expression mouse profiling of prostates of 3 month WT, ERG, PTEN f/f and Pten f/f;ERG mice. For WT and ERG prostates, entire prostates were dissected and total RNA immediated harvested. For Pten f/f and Pten f/f;ERG prostates, the Ventral Lobe was dissected.