Project description:Epigenetic alterations contribute to leukemogenesis in childhood acute myeloid leukemia (AML). We used RNAi screens of AML cells together with non-transformed bone marrow cells and identified CHD4 as being required for AML maintenance. RNAi and CRISPR-Cas9 approaches, showed that CHD4 is essential for cell growth of leukemic cells in vitro, and disease progression in vivo, including primary childhood AML cells. Loss of function of CHD4 arrests AML cells in the G0 phase of the cell cycle, which is associated with downregulation of MYC and its target genes. Conversely, CHD4 suppression is not essential for normal blood cells. Taken together, our results identify CHD4 as a potential therapeutic target in childhood AML.
Project description:RNA-seq dataset of TRAFD1 knockdown in THP-1 cell lines compared to THP1 cell lines treated with non targeting siRNA (SCR) and untreated cells (WT), under unstimulated and stimulated (LPS) conditions.
Project description:We performed a label-free LC-MS/MS study to analyse the role of Chd4 regulation in MuSC in suppressing genes enabling programmed cell death as part of the muscle regeneration program. Lox-cre recombination was used to create a deletion mutant of the CHD4 chromatin modifier (exons 12-21). A pseudo "infection" with GFP was used as control. Proteomics analysis here serves as a method to compare the differentially deregulated proteins upon knockdown of Chd4 in MuSCs using Adenoviral CRE recombination.
Project description:RNA-seq upon TBX2 knockdown in the neuroblastoma cell line CLB-GA. Cells were transduced with two different shRNAs (sh#2 and sh#4) targeting TBX2 and a non-targeting control (NTC), and selected with puromycin. Analysis was performed seven days upon TBX2 knockdown, including three biological replicates per condition.
Project description:Transcriptome analysis of prostate cancer patient derived organoid DU145 cell line upon knockdown of YAP, TAZ, or YAP/TAZ mediated by siRNAs
Project description:RNA-seq upon TBX2, MYCN or combination of TBX2 and MYCN knockdown in the neuroblastoma cell line IMR-5/75. Cells were transduced with two different shRNAs (shTBX2_2 and shTBX2_4) targeting TBX2 and a non-targeting control (NTC), and selected with puromycin. Cells were treated with doxycycline for shMYCN induction (with DOX or not). Analysis was performed three days upon TBX2 knockdown and two days upon MYCN knockdown, including six biological replicates per condition.
Project description:To understand the role of the nucleosome remodelling protein CHD4 in regulating spermatogonial stem cell function, we performed single cell RNA-sequencing on undifferentiated spermatogonia from primary culture that had been transfected with either control (non-targeting) siRNA or Chd4 siRNA. Transcriptome profiling revealed reduced expression of ‘self-renewal’ genes following Chd4 knockdown, along with increased expression of signature progenitor genes. Overall, CHD4 was demonstrated to primarily act as an activator of gene expression in SSCs. In pairing these data with additional analyses, including use of an Id4-eGfp transgenic mouse line, spermatogonial transplantation, and co-immunoprecipitation experiments: the findings of our study demonstrated a previously unappreciated and fundamental role for CHD4 in controlling fate decisions in the spermatogonial pool.