Pbrm1 regulates interferon signaling in mouse AML
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA869695 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pbrm1 regulates interferon signaling in mouse AML [RNA-seq HAP1]
| PRJNA869699 | ENA
Project description:Pbrm1 regulates interferon signaling in mouse AML [RNA-seq Mouse]
| PRJNA869700 | ENA
Project description:Pbrm1 regulates interferon signaling in mouse AML [ChIP-seq HAP1]
| PRJNA869701 | ENA
Project description:CRISPR/Cas9 screening approaches are powerful tools to identify in vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which sequential acquisition of somatic mutations generates clonal diversity. With time, additional cooperating mutations may drive disease progression. Using an in vivo pooled genetic mutagenesis screen of epigenetic factors in primary murine HSPCs, we sought to uncover unrecognized genes that contribute to leukemia progression. We first modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs followed by transplantation. We then performed pooled mutagenesis of genes encoding epigenetic factors and identified Pbrm1/Baf180, a subunit of polybromo (PBAF) SWI/SNF chromatin remodeling complex, as a negative driver of disease progression. We found that Pbrm1 loss promoted leukemogenesis with significantly shortened latency. Pbrm1-deficient AML cells were less immunogenic, and characterized by attenuated interferon signaling and reduced MHC II expression. We explored potential relevance to human leukemia by assessing the involvement of Pbrm1 in control of interferon pathway components and found that Pbrm1 binds at promoters of a subset of these genes, and most notably at IRF1, which in turn regulates in MHC II expression. Our findings revealed a novel role of Pbrm1 in leukemia progression. More generally, CRISPR/Cas9 screening, coupled with phenotypic readouts in vivo, has revealed a pathway by which transcriptional control of interferon signaling influences leukemia cell interactions with the immune system.
2023-07-12 | GSE211260 | GEO
Project description:CRISPR/Cas9 screening approaches are powerful tools to identify in vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which sequential acquisition of somatic mutations generates clonal diversity. With time, additional cooperating mutations may drive disease progression. Using an in vivo pooled gene editing screen of epigenetic factors in primary murine hematopoietic stem and progenitor cells (HSPCs), we sought to uncover unrecognized genes that contribute to leukemia progression. We first modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs followed by transplantation. We then performed pooled CRISPR/Cas9 editing of genes encoding epigenetic factors and identified Pbrm1/Baf180, a subunit of polybromo BRG1/BRM-associated factor (PBAF) SWI/SNF chromatin remodeling complex, as a negative driver of disease progression. We found that Pbrm1 loss promoted leukemogenesis with significantly shortened latency. Pbrm1-deficient leukemia cells were less immunogenic, and characterized by attenuated interferon signaling and reduced MHC II expression. We explored potential relevance to human leukemia by assessing the involvement of PBRM1 in control of interferon pathway components and found that PBRM1 binds at promoters of a subset of these genes, and most notably at IRF1, which in turn regulates MHC II expression. Our findings revealed a novel role of Pbrm1 in leukemia progression. More generally, CRISPR/Cas9 screening, coupled with phenotypic readouts in vivo, has identified a pathway by which transcriptional control of interferon signaling influences leukemia cell interactions with the immune system.
2023-07-12 | GSE211262 | GEO
Project description:CRISPR/Cas9 screening approaches are powerful tools to identify in vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which sequential acquisition of somatic mutations generates clonal diversity. With time, additional cooperating mutations may drive disease progression. Using an in vivo pooled gene editing screen of epigenetic factors in primary murine hematopoietic stem and progenitor cells (HSPCs), we sought to uncover unrecognized genes that contribute to leukemia progression. We first modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs followed by transplantation. We then performed pooled CRISPR/Cas9 editing of genes encoding epigenetic factors and identified Pbrm1/Baf180, a subunit of polybromo BRG1/BRM-associated factor (PBAF) SWI/SNF chromatin remodeling complex, as a negative driver of disease progression. We found that Pbrm1 loss promoted leukemogenesis with significantly shortened latency. Pbrm1-deficient leukemia cells were less immunogenic, and characterized by attenuated interferon signaling and reduced MHC II expression. We explored potential relevance to human leukemia by assessing the involvement of PBRM1 in control of interferon pathway components and found that PBRM1 binds at promoters of a subset of these genes, and most notably at IRF1, which in turn regulates MHC II expression. Our findings revealed a novel role of Pbrm1 in leukemia progression. More generally, CRISPR/Cas9 screening, coupled with phenotypic readouts in vivo, has identified a pathway by which transcriptional control of interferon signaling influences leukemia cell interactions with the immune system.
2023-07-12 | GSE211261 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-07-11 | GSE211263 | GEO
Project description:Long noncoding RNA INCA1 regulates tumor interferon signaling.
| PRJNA565715 | ENA
Project description:Long noncoding RNA INCA1 regulates tumor interferon signaling
| PRJNA565585 | ENA
Project description:Tumor interferon signaling regulates the expression of immunosuppressive molecules and promotes cancer immune evasion. Although the role of long noncoding RNAs (lncRNAs) in the regulation of gene expression is now emerging, their function in tumor interferon signaling remains unexplored. We have identified the interferon-γ (IFNγ)-stimulated non-coding RNA 1 (INCA1) as a novel lncRNA expressed form the PD-L1 locus. INCA1 is expressed in multiple tumor types and its levels increase after IFNγ stimulation. In this study we performed transcriptome analysis (RNA-seq) of INCA1 knockdown cells and show that INCA1 regulates the expression of several interferon-stimulated genes. Overall, our findings reveal INCA1 as a critical component of the tumor interferon signaling.
2020-07-29 | GSE137454 | GEO