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Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE126264 | GEO | 2019/02/07

REPOSITORIES: GEO

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Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis.

Project description:The BCL6 Corepressor (BCOR) is a component of a variant Polycomb repressive complex 1 (PRC1) that is essential for normal development. Recurrent mutations in the BCOR gene have been identified in acute myeloid leukaemia and myelodysplastic syndrome among other cancers; however, its function remains poorly understood. Here we examine the role of BCOR in haematopoiesis in vivo using a conditional mouse model that mimics the mutations observed in haematological malignancies. Inactivation of Bcor in haematopoietic stem cells (HSCs) results in expansion of myeloid progenitors and co-operates with oncogenic KrasG12D in the initiation of an aggressive and fully transplantable acute leukaemia. Gene expression analysis and chromatin immunoprecipitation sequencing reveals differential regulation of a subset of PRC1-target genes including HSC-associated transcription factors such as Hoxa7/9. This study provides mechanistic understanding of how BCOR regulates cell fate decisions and how loss of function contributes to the development of leukaemia.

| S-EPMC6430802 | biostudies-literature

Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [TargetedCRISPRscreen]

Project description:Investigating Bcor target genes in BcorΔE9-10KrasG12D leukaemia with a custom CRISPR dropout screen

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

Project description:Investigation of the epigenetic profile induced by Bcor loss

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

Project description:Investigation of the transcriptional consequences of Bcor loss in bone marrow transplant

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

Project description:Investigation of the transcriptional profile of BcorΔE9-10KrasG12D myeloid progenitors

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

Project description:Investigation of the transcriptional changes in BcorΔE9-10KrasG12D myeloid progenitors

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

Project description:Investigation of the chromatin accessibility in myeloid progenitor cells

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Project description:Investigation of the gene expression changes induced by Bcor loss in myeloid progenitors

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Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis

Project description:Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis

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Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis [TargetedCRISPRscreen]

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

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