Loss of RUNX1 favors mesenchymal stem cells development at the expense of hematopoiesis in hPSC-derived hematopoiesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA971128 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBP-beta prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies. Microarray expression data obtained from differentiating murine hematopoietic cells, 3 independent biological replicates (measured twice) from iRUNX1 culture -/+DOX induction
2013-02-11 | E-GEOD-39662 | biostudies-arrayexpress
Project description:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBPM-NM-2 prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies. ChIPseq data from transcription factors Runx1, Fli-1, Scl/Tal1 and C/EBPM-NM-2, histone modification H3K9Ac as well as RNA Pol II obtained from differentiating murine hematopoietic cells
2012-10-18 | E-GEOD-40235 | biostudies-arrayexpress
Project description:our work established a powerful method for physically studying TF-RNA interaction in very few cells, and provide valuable recourse for decoding more precious regulatory network of Runx1 during embryonic hematopoiesis.
2022-08-26 | GSE211847 | GEO
Project description:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBPβ prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies.
2012-10-18 | GSE40235 | GEO
Project description:Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBP-beta prime hematopoietic genes and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies.
2013-02-11 | GSE39662 | GEO
Project description:Despite absent expression in normal hematopoiesis, the Forkhead factor FOXC1, a critical mesenchymal differentiation regulator, is highly expressed in ~30% of HOXAhigh AML to confer blocked monocyte/macrophage differentiation. Through integrated proteomics and bioinformatics, we discovered that FOXC1 and RUNX1 interact through Forkhead and Runt domains respectively and cooccupy primed and active enhancers distributed close to differentiation genes. FOXC1 stabilises association of RUNX1, HDAC1 and Groucho repressor TLE3 to limit enhancer activity: FOXC1 knockdown induced loss of repressor proteins, gain of CEBPA binding, enhancer acetylation and upregulation of nearby genes, including KLF2. Furthermore, it triggered genome-wide redistribution of RUNX1, TLE3 and HDAC1 from enhancers to promoters leading to repression of self-renewal genes including MYC and MYB. Our studies highlight RUNX1 and CEBPA transcription factor swapping as a feature of leukemia cell differentiation, and reveal that FOXC1 prevents this by stabilising enhancer binding of a RUNX1/HDAC1/TLE3 transcription repressor complex, to oncogenic effect.
2021-08-08 | PXD027740 | Pride
Project description:Targeted disruption of the Runx1/ AML1 gene in mice has demonstrated that it is required for the emergence of definitive hematopoietic cells, but that it is not essential for the formation of primitive erythrocytes. These findings led to the conclusion that Runx1 is a stage-specific transcription factor acting only during definitive hematopoiesis. However, the zebrafish and Xenopus homologues of Runx1 have been shown to play roles in primitive hematopoiesis, suggesting that mouse Runx1 might also be involved in the development of primitive lineages. In order to identify differentially expressed genes in runx1-/- primitive erythroid, we carried out microarray analysis. Experiment Overall Design: Total RNA from E10.5 wild type and Runx1â??/â?? yolk sacs was extracted, and gene expression patterns were compared.
2008-06-11 | E-GEOD-10348 | biostudies-arrayexpress
Project description:Mutations of RUNX1 are detected in patients with myelodysplastic syndrome (MDS). In particular, C-terminal truncation mutations lack a transcription regulatory domain and have increased DNA binding through the runt homology domain (RHD). The expression of the RHD, RUNX1(41-214), in mouse hematopoietic cells induced progression to MDS and acute myeloid leukemia (AML). Analysis of pre-myelodysplastic animals revealed expansion of c-Kit+Sca-1+Lin- (KSL) cells and skewed differentiation to myeloid at the expense of the lymphoid lineage. These abnormalities correlate with the phenotype of Runx1-deficient animals, as expected given the reported dominant-negative role of C-terminal mutations over the full-length RUNX1. However, MDS is not observed in Runx1-deficient animals. Gene expression profiling revealed that RUNX1(41-214) KSLs have an overlapping yet distinct gene expression profile from Runx1-deficient animals. Moreover, an unexpected parallel was observed between the hematopoietic phenotype of RUNX1(41-214) and aged animals. Genes deregulated in RUNX1(41-214), but not in Runx1-deficient animals, were inversely correlated with the aging gene signature of hematopoietic stem cells (HSC), suggesting that disruption of the expression of genes related to normal aging by RUNX1 mutations contributes to development of MDS. The data presented here provide insights into the mechanisms of development of MDS in HSCs by C-terminal mutations of RUNX1. Gene expression analysis were performed on c-Kit+/Sca-1+/Lin-/IL7Ra- (KSL) cells sorted from RUNX1(41-214)-expressing and Runx1-knockout (Runx1floxed/floxed MxCre+/-) and control mice (Runx1floxed/floxedMxCre-/-).
2012-11-29 | E-GEOD-40155 | biostudies-arrayexpress
Project description:Targeted disruption of the Runx1/ AML1 gene in mice has demonstrated that it is required for the emergence of definitive hematopoietic cells, but that it is not essential for the formation of primitive erythrocytes. These findings led to the conclusion that Runx1 is a stage-specific transcription factor acting only during definitive hematopoiesis. However, the zebrafish and Xenopus homologues of Runx1 have been shown to play roles in primitive hematopoiesis, suggesting that mouse Runx1 might also be involved in the development of primitive lineages. In order to identify differentially expressed genes in runx1-/- primitive erythroid, we carried out microarray analysis. Keywords: genetic modification
2008-02-02 | GSE10348 | GEO