Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice

ABSTRACT: Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice

PROVIDER: PRJNA663660 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12649000_1.fastq.gz	Fastqsanger.gz
	SRR12649000_2.fastq.gz	Fastqsanger.gz
	SRR12648981_1.fastq.gz	Fastqsanger.gz
	SRR12648981_2.fastq.gz	Fastqsanger.gz
	SRR12648982_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 40

Similar Datasets

Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice.

Project description:Recurrent loss-of-function mutations of BCL6 co-repressor (BCOR) gene are found in about 4% of AML patients with normal karyotype and are associated with DNMT3a mutations and poor prognosis. Therefore, new anti-leukemia treatments and mouse models are needed for this combinatorial AML genotype. For this purpose, we first generated a Bcor-/- knockout mouse model characterized by impaired erythroid development (macrocytosis and anemia) and enhanced thrombopoiesis, which are both features of myelodysplasia/myeloproliferative neoplasms. We then created and characterized double Bcor-/-/Dnmt3a-/- knockout mice. Interestingly, these animals developed a fully penetrant acute erythroid leukemia (AEL) characterized by leukocytosis secondary to the expansion of blasts expressing c-Kit+ and the erythroid marker Ter119, macrocytic anemia and progressive reduction of the thrombocytosis associated with loss of Bcor alone. Transcriptomic analysis of double knockout bone marrow progenitors revealed that aberrant erythroid skewing was induced by epigenetic changes affecting specific transcriptional factors (GATA1-2) and cell-cycle regulators (Mdm2, Tp53). These findings prompted us to investigate the efficacy of demethylating agents in AEL, with significant impact on progressive leukemic burden and mice overall survival. Information gained from our model expands the knowledge on the biology of AEL and may help designing new rational treatments for patients suffering from this high-risk leukemia.

| S-EPMC8257496 | biostudies-literature

Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice

Project description:Recurrent loss-of-function mutations of BCL6 co-repressor (BCOR) gene are found in about 4% of AML patients with normal karyotype and are associated with DNMT3a mutations and poor prognosis. Therefore, new anti-leukemia treatments and mouse models are needed for this combinatorial AML genotype. For this purpose, we first generated a Bcor-/- knock-out mouse model characterized by impaired erythroid development (macrocytosis and anemia) and enhanced thrombopoiesis, which are both features of myelodysplasia/myeloproliferative neoplasms. We then created and characterized double Bcor-/-/Dnmt3a-/- knock-out mice. Interestingly, these animals developed a fully penetrant acute erythroid leukemia (AEL) characterized by leukocytosis secondary to the expansion of blasts expressing c-Kit+ and the erythroid marker Ter119, macrocytic anemia and progressive reduction of the thrombocytosis associated with loss of Bcor alone. Transcriptomic analysis of double knock-out bone marrow progenitors revealed that aberrant erythroid skewing was induced by epigenetic changes affecting specific transcriptional factors (GATA1-2) and cell-cycle regulators (Mdm2, Tp53). These findings prompted us to investigate the efficacy of demethylating agents in AEL, with significant impact on progressive leukemic burden and mice overall survival. Information gained from our model expands the knowledge on the biology of AEL and may help designing new rational treatments for patients suffering from this high-risk leukemia.

2021-09-01 | GSE158018 | GEO

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis

Project description:Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis

| PRJNA521420 | ENA

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [TargetedCRISPRscreen]

Project description:Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [TargetedCRISPRscreen]

| PRJNA521244 | ENA

Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis

Project description:Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, SCL/TAL1 and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary megakaryocytes (MEG) and erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, SCL/TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-specific cis-regulatory modules in multipotential hematopoietic progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming occurs is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential precursor via overlapping and divergent functions of shared hematopoietic transcription factors. Gene expression changes during the development of primary megakaryocytes (MEG) and erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells

2013-08-09 | E-GEOD-49664 | biostudies-arrayexpress

Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis

Project description:Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary cultured megakaryocytes (MEG) and primary erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-associated cis-regulatory modules (CRMs) in multipotential progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential progenitor via overlapping and divergent functions of shared hematopoietic transcription factors. Genome-wide chromatin occupancy using ChIP-seq on 4 transcription factors (GATA1, GATA2, TAL1, and FLII) and three histone marks (H3K4me1, H3K4me3, and H3K27me3) in lineage-commited primary erythoblasts (ERY) and primary cultured megakaryocytes (MEG).

2014-11-14 | E-GEOD-51337 | biostudies-arrayexpress

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [BcorKrasChIP-seq]

Project description:Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [BcorKrasChIP-seq]

| PRJNA521242 | ENA

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [BcorKrasRNA-seq]

Project description:Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [BcorKrasRNA-seq]

| PRJNA521245 | ENA

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [TransplantRNA-SEQ]

Project description:Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [TransplantRNA-SEQ]

| PRJNA521248 | ENA

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [20wRNA-seq]

Project description:Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [20wRNA-seq]