Ontology highlight
ABSTRACT:
PROVIDER: PRJNA574055 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10177320.fastq.gz | Fastqsanger.gz | |||
| SRR10177321.fastq.gz | Fastqsanger.gz | |||
| SRR10177322.fastq.gz | Fastqsanger.gz | |||
| SRR10177323.fastq.gz | Fastqsanger.gz | |||
| SRR10177324.fastq.gz | Fastqsanger.gz |
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Project description:Epigenetic regulation by the SWI/SNF complex is essential for normal self-renewal capacity and pluripotency of human pluripotent stem cells (hPSCs). It has been shown that different subunits of the complex have a distinct role in this regulation. Specifically, the SMARCB1 core subunit has been shown to regulate the activity of enhancers in diverse types of cells, including hPSCs. Here we report the establishment of conditional hPSC lines, which enable the control of SMARCB1 expression from complete loss of function (LOF) to significant overexpression. Using this system, we show that any deviation from normal SMARCB1 expression leads to rapid differentiation of the cells. We further found that SMARCB1 expression is not required for the differentiation of hPSCs into progenitor cells of the three germ layers, but rather for later stages of differentiation. Moreover, we identify SMARCB1 as a critical player in the regulation of cell-cell and cell-extracellular matrix (ECM) interactions in hPSCs. Finally, our results show that complete SMARCB1 LOF affects hPSC fate in a different way than the effect of partial downregulation of the gene and thus emphasizes the complex regulation of hPSCs by SMARCB1.
2020-10-01 | GSE158842 | GEO
Project description:To identify DNA accessibility targets regulated by the SWI/SNF subunit SMARCB1 in bladder cancer, we compared the ATAC-seq signals in T24 cells engineered for SMARCB1 knockout, non-targeting control, or SMARCB1 re-expression following knockout. Analysis of altered DNA accessibility profiles revealed new roles for SMARCB1 in the regulation of gene expression in bladder cancer, and suggested new therapeutic opportunities.
2023-11-17 | GSE213964 | GEO
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development. Two cancer cell lines, 167 and 365, derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice were re-infected with a retro-viral vector for Smarcb1 re-expression or an empty retro-viral vector as control. Total-RNA was collected 3 days post infection so as to enrich for direct targets of Smarcb1 transcriptionaly regulated genes
2013-12-31 | E-GEOD-46017 | biostudies-arrayexpress
Project description:Stem cell fate decisions are tightly regulated by several processes, including epigenetic based histone modifications. Histone variants (HVs) represent a subfamily of epigenetic regulators implicated in early embryonic development, but their role in stem cell fate control has not been targeted. Here we reveal direct involvement of phosphorylation state of the histone variant H2A.X that allows control of self-renewal and differentiation of human pluripotent stem cells (hPSCs) and leukemic patient derived progenitors. Reduced levels of γH2A.X using either genetic approaches or chemical targeting allowed enhanced hPSC differentiation toward the mesodermal (hematopoietic) lineage with concomitant inhibition of ectodermal (neural) development. In contrast, activation and sustained levels of phosphorylated H2A.X enhanced hPSC ectodermal fate while suppressing mesodermal derived hematopoiesis. This controlled bifurcation of neural vs. hematopoietic differentiation correlated to occupancy of γH2A.X at gene loci associated with lineage selection. Drug modulation of H2A.X phosphorylation was extended to somatic cells to reveal the ability to induce differentiation of leukemic progenitors and serve as a biomarker in a cohort of adult leukemic patients. Our study uncovers a mechanism of cell-fate control of hPSCs extended to neoplastic progenitors through a histone variant epigenetic regulation
2021-03-09 | GSE164680 | GEO
Project description:The aim of this study is to analyze the change in genome wide expression levels in HAP1 cells upon loss of SMARCB1, SMARCA4 or both these genes together. The SMARCB1 and SMARCA4 genes were the hits from a genome wide screen involving genetrap mutagenesis to find new players that are involved in sensitivity to Doxorubicin (Dox). It was found that loss of SMARCB1 and SMARCA4 genes impart resistance in HAP1 cells to Dox. To validate this, the genes were knocked out in HAP1 cells with CRISPR-Cas9 technology. Gene expression levels in SMARCB1 null, SMARCA4 null and SMARCB1-SMARCA4 double null cells were compared to wildtype HAP1 cells using RNAseq. From these experiments it was found that SMARCB1 loss caused several fold increase in ABCB1 gene levels. ABCB1 is an efflux pump in cells responsible for flushing out many small-molecule drugs. Further analysis of this gene confirmed that ABCB1 was the main factor responsible for Dox resistance upon SMARCB1 loss. In total there are four different cell types with two replicates for each cell type. Therefore, 8 samples in total.
2016-08-22 | E-GEOD-75515 | biostudies-arrayexpress
Project description:The multi-subunit ATP-dependent chromatin remodeling complex BAF ('mammalian SWI/SNF complex') regulates DNA accessibility during cell fate transitions and functions as a context-dependent tumor suppressor. SMARCB1, as a one of the component of BAF complex, was first found to be biallelically inactivated in ~98% of all malignant rhabdoid tumors (MRT), aggressive pediatric tumors that can occur cranially or extracranially. To examine the mechanisms through which inactivation of SMARCB1 drives malignant rhabdoid tumorigenesis, we conducted RNAseq studies in BT-12 cells reconstituted with either WT or M4 mutant (an in-frame deletion (185-193D) was identified from tumor patient) SMARCB1. These results indicate that loss of SMARCB1 promotes cell proliferation but also impairs cell adhesion and migration, consistent with the hypothesis that SMARCB1 exerts its tumor suppressive function predominantly by inhibiting proliferation. We applied the RNA-Seq to provide the transcriptomic profiling of BT-12 cell lines without or with stable expression of SMARCB1.
2020-10-01 | GSE139262 | GEO
Project description:Genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are mutated in >20% of cancers. SWI/SNF complexes exist in three distinct families that each contribute to regulation of transcription, although the functional interactions between the families are not well understood. Rhabdoid tumors constitute an informative model system as these highly aggressive cancers are driven by inactivation of a single SWI/SNF subunit, SMARCB1, which is present in two SWI/SNF families (cBAF and PBAF) but not in the third (GBAF/ncBAF). We and others have shown that BRD9, a therapeutically targetable member of ncBAF, is essential specifically in SMARCB1-deficient cancers, suggesting key functional relationships between SMARCB1-containing complexes and BRD9/ncBAF. However, the mechanistic underpinnings of these relationships are poorly understood. Here, we demonstrate that genomic binding of BRD9 is largely dependent upon SMARCB1 such that the absence of SMARCB1 results in significantly reduced BRD9 binding. At select sites, however, we show that SMARCB1-loss results in gain of BRD9 binding and BRD9-dependent accessibility. We find that this gain is associated with expression of genes promoting cell migration. Our results define relationships between SWI/SNF complex families, elucidate mechanisms by which SMARCB1 loss drives oncogenesis, and provide mechanistic insight into the synthetic-lethal relationship between SMARCB1 and BRD9.
2023-07-14 | GSE210632 | GEO
Project description:Genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are mutated in >20% of cancers. SWI/SNF complexes exist in three distinct families that each contribute to regulation of transcription, although the functional interactions between the families are not well understood. Rhabdoid tumors constitute an informative model system as these highly aggressive cancers are driven by inactivation of a single SWI/SNF subunit, SMARCB1, which is present in two SWI/SNF families (cBAF and PBAF) but not in the third (GBAF/ncBAF). We and others have shown that BRD9, a therapeutically targetable member of ncBAF, is essential specifically in SMARCB1-deficient cancers, suggesting key functional relationships between SMARCB1-containing complexes and BRD9/ncBAF. However, the mechanistic underpinnings of these relationships are poorly understood. Here, we demonstrate that genomic binding of BRD9 is largely dependent upon SMARCB1 such that the absence of SMARCB1 results in significantly reduced BRD9 binding. At select sites, however, we show that SMARCB1-loss results in gain of BRD9 binding and BRD9-dependent accessibility. We find that this gain is associated with expression of genes promoting cell migration. Our results define relationships between SWI/SNF complex families, elucidate mechanisms by which SMARCB1 loss drives oncogenesis, and provide mechanistic insight into the synthetic-lethal relationship between SMARCB1 and BRD9.
2023-07-14 | GSE210633 | GEO
Project description:Our data demonstrated an unprecedented role of RUNX1 in regulating hematopoietic and mesenchymal fate decisions in human pluripotent stem cells (hPSC)-derived hematopoiesis
2024-05-17 | GSE232147 | GEO
Project description:In vivo differentiation of human pluripotent stem cells (hPSCs) has unique advantages such as multilineage differentiation, angiogenesis, and close cell‒cell interactions. To systematically investigate the multilineage differentiation mechanisms of hPSCs, we constructed the in vivo hPSC differentiation landscape containing 239,670 cells using teratoma models. We inferred 18 cell differentiation trajectories and characterized common and specific gene regulation patterns during hPSC differentiation at both transcriptional and epigenetic levels. The results of developing single cell Basic Local Alignment Search Tool (dscBLAST), our self-developed tool for cell identification and developmental stage speculation, further confirmed the differentiated cell identity and suggested that cells in the teratoma are largely at immature developmental stages. Overall, our study offers new insights into stem cell fate decisions and embryonic development; dscBLAST shows favorable cell identification performance, providing both developmental and adult cells with a powerful tool for cell annotation and stage speculation.
2022-10-28 | GSE216323 | GEO