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A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [10x scRNAseq]

ABSTRACT: RUNX1 is crucial for multiple stages of hematopoiesis and its mutation can cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). We aim to study the role of RUNX1 in megakaryocyte-biased HSCs differentiation to megakaryocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE211861 | GEO | 2023/01/20

REPOSITORIES: GEO

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A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [Single MK RNAseq]

2023-01-20 | GSE211937 | GEO

A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [RNA-seq]

Project description:RUNX1 is crucial for multiple stages of hematopoiesis and its mutation can cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). We aim to study the role of RUNX1 in megakaryocyte-biased HSCs differentiation to megakaryocytes. Here, by using Runx1F/FMx1-Cre mouse model, we sorted CD41pos HSCs and CD41neg HSCs in both RUNX1 WT and KO, and compared their gene expression profiles.

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A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [CUT&RUN Chip-seq]

Project description:RUNX1 is crucial for multiple stages of hematopoiesis and its mutation can cause familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). We aim to study the role of RUNX1 in megakaryocyte-biased HSCs differentiation to megakaryocytes. Here, by using Runx1F/FMx1-Cre mouse model ,we sorted CD41pos HSCs and CD41neg HSCs in both RUNX1 WT and KO, and tested the RUNX1 direct binding targets in these cells genome.

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Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (expression)

Project description:RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 andÂ p300Â identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif.Â The data providesÂ the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK,Â unravels the Runx1-regulated program controlling MK maturationÂ in vivoÂ andÂ identifies itsÂ bona fideÂ regulated genes. It advances our understandingÂ of the molecular events that upon mutations in RUNX1 lead to theÂ predisposition to familial platelet disorders and FPD-AML. Gene expression profiles of mature megakaryocytes taken from fetal livers of megakaryocyte-specific Runx1 knockout mice, using Runx1F/F/Pf4-Cre mice versus control (WT) mice.

2013-03-22 | E-GEOD-45373 | biostudies-arrayexpress

A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [10x scRNAseq]

Project description:A Critical Role of RUNX1 in Governing Megakaryocyte-Primed Hematopoietic Stem Cell Differentiation [10x scRNAseq]

| PRJNA872402 | ENA

Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (ChIP-seq)

Project description:RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 andÂ p300Â identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif.Â The data providesÂ the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK,Â unravels the Runx1-regulated program controlling MK maturationÂ in vivoÂ andÂ identifies itsÂ bona fideÂ regulated genes. It advances our understandingÂ of the molecular events that upon mutations in RUNX1 lead to theÂ predisposition to familial platelet disorders and FPD-AML. Examination of RUNX1 and P300 binding in WT mouse megakaryoctye cells using ChIP-Seq. The supplementary 'GSE45372_PeakList.txt' file includes a list of regions identified as binding for P300 or RUNX1 or both.

2013-03-22 | E-GEOD-45372 | biostudies-arrayexpress

Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (expression)

Project description:RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 and p300 identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif. The data provides the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK, unravels the Runx1-regulated program controlling MK maturation in vivo and identifies its bona fide regulated genes. It advances our understanding of the molecular events that upon mutations in RUNX1 lead to the predisposition to familial platelet disorders and FPD-AML.

2013-03-22 | GSE45373 | GEO

Cell-autonomous function of Runx1 transcriptionally regulates megakaryocytic maturation in mice (ChIP-seq)

Project description:RUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 and p300 identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif. The data provides the first example of genome-wide Runx1/p300 occupancy in maturating FL-MK, unravels the Runx1-regulated program controlling MK maturation in vivo and identifies its bona fide regulated genes. It advances our understanding of the molecular events that upon mutations in RUNX1 lead to the predisposition to familial platelet disorders and FPD-AML.

2013-03-22 | GSE45372 | GEO

GFI1B and LSD1 repress myeloid traits during megakaryocyte differentiation

Project description:The transcription factor Growth Factor Independence 1B (GFI1B) recruits Lysine Specific Demethylase 1A (LSD1/KDM1A) to stimulate gene programs relevant for megakaryocyte and platelet biology. Inherited pathogenic GFI1B variants result in thrombocytopenia and bleeding propensities with varying intensity. Whether these affect similar gene programs is unknow. Here we studied transcriptomic effects of four patient-derived GFI1B variants (GFI1BT174N,H181Y,R184P,Q287*) in MEG01 megakaryoblasts. Compared to normal GFI1B, each variant affected different gene programs with GFI1BQ287* uniquely failing to repress myeloid traits. In line with this, single cell RNA-sequencing of induced pluripotent stem cell (iPSC)-derived megakaryocytes revealed a 4.5-fold decrease in the megakaryocyte/myeloid cell ratio in GFI1BQ287* versus normal conditions. Inhibiting the GFI1B-LSD1 interaction with small molecule GSK-LSD1 resulted in activation of myeloid genes in normal iPSC-derived megakaryocytes similar as observed for GFI1BQ287* iPSC-derived megakaryocytes. Thus, GFI1B and LSD1 facilitate gene programs relevant for megakaryopoiesis while simultaneously repressing programs that induce myeloid differentiation.

2024-03-28 | PXD050401 | Pride

Characterisation of the mouse megakaryocyte transcriptome

Project description:This study aims to identify all genes expressed in primary mouse megakaryocytes Keywords: Megakaryocyte, SAGE, transcriptome analysis Mouse megakaryocytes were grown in vitro from bone marrow progenitors. Mature, polyploid (approximately 95% 64n and 128n) differentiated megakaryocytes were used to generate RNA for SAGE library construction.

2007-02-02 | E-GEOD-6940 | biostudies-arrayexpress

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