Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA92003 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease of the hematopoietic system, which is caused by heterozygous mutations in RUNX1. FPD/AML patients have a bleeding disorder characterized by thrombocytopenia with reduced platelet numbers and functions, and a tendency to develop AML. Currently no suitable animal models exist for FPD/AML as Runx1+/- mice and zebrafish do not develop bleeding disorders or leukemia. Here we derived induced pluripotent stem cells (iPSCs) from two patients in a family with FPD/AML, and found that the FPD iPSCs display defects in megakaryocytic differentiation in vitro. We corrected the RUNX1 mutation in one FPD iPSC line through gene targeting, which led to normalization of megakaryopoiesis of the iPSCs in culture. Our results demonstrate successful in vitro modeling of FPD with patient-specific iPSCs and confirm that RUNX1 mutations are responsible for megakaryopoietic defects in FPD patients.
2014-07-01 | GSE54295 | GEO
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.
2023-01-20 | GSE211937 | GEO
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.
2023-01-20 | GSE211861 | GEO
Project description:Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease of the hematopoietic system, which is caused by heterozygous mutations in RUNX1. FPD/AML patients have a bleeding disorder characterized by thrombocytopenia with reduced platelet numbers and functions, and a tendency to develop AML. Currently no suitable animal models exist for FPD/AML as Runx1+/- mice and zebrafish do not develop bleeding disorders or leukemia. Here we derived induced pluripotent stem cells (iPSCs) from two patients in a family with FPD/AML, and found that the FPD iPSCs display defects in megakaryocytic differentiation in vitro. We corrected the RUNX1 mutation in one FPD iPSC line through gene targeting, which led to normalization of megakaryopoiesis of the iPSCs in culture. Our results demonstrate successful in vitro modeling of FPD with patient-specific iPSCs and confirm that RUNX1 mutations are responsible for megakaryopoietic defects in FPD patients. Here, we derived iPSCs from two FPD/AML patients and demonstrated that these iPSCs have a megakaryopoietic defect in culture. Importantly we were able to rescue the megakaryopoietic defect by correcting the RUNX1 mutation with a gene targeting strategy enhanced by zinc finger nucleases (ZFNs). Three independent samples were obtained for each time point.
2014-07-01 | E-GEOD-54295 | biostudies-arrayexpress
Project description:Characterize the genes deregulated in CD34 positive cells from peripheral blood of FPD/AML patients harbouring two different RUNX1 mutations. RUNX1 (also called AML1), a DNA-binding subunit of the CBF transcription factor family, is a master regulatory gene in hematopoiesis and acts as a tumour suppressor. Heterozygous germ line alterations in RUNX1 lead to a familial platelet disorder with a propensity to develop acute myeloid leukemia (FPD/AML). Although RUNX1 abnormalities per se are not sufficient to induce full-blown leukemia in FPD, this pathology represents a valuable model to understand how RUNX1 germ line mutations predispose to acquisition of additional genetic changes leading to leukemia transformation. To investigate how RUNX1 may predispose to leukemia, we performed a comparative study between two pedigrees harbouring different RUNX1 mutations, one associated with only thrombocytopenia (R139stop) and the other leading to thrombocytopenia and leukemic predisposition (R174Q).
2010-09-11 | E-TABM-792 | biostudies-arrayexpress
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.
2023-01-20 | GSE211935 | GEO
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. 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
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. 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
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.
2023-01-20 | GSE212001 | GEO
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