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EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism

ABSTRACT: EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism

PROVIDER: PRJNA781462 | ENA |

REPOSITORIES: ENA

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EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [10x]

Project description:Haematopoietic stem cells (HSC) and multipotent progenitor cells (MPP) generate all cells of the blood system, although cellular heterogeneity and bias in lineage potential have been observed. Here, we examined whether lineage-specific transcription factors, such as the B-lineage determinant EBF1, establish lineage bias in early progenitors. We detect low level EBF1 expression in myeloid-biased MPP3 and lymphoid-biased MPP4 cells, and show that Ebf1-deficient animals display reduced HSC quiescence and repopulation capacity, enhanced myelopoiesis and enhanced myeloid differentiation potential of MPP3 and MPP4 cells. Bulk and single-cell RNA-seq analysis revealed a CEBPa-driven myeloid transcriptome in Ebf1-deficient progenitors, and we find that EBF1 binds and potentially antagonizes the haematopoietic Cebpa enhancer. In MPP3 cells, EBF1 additionally primes enhancers associated with B-lymphoid genes that gain expression in common lymphoid progenitors. Thus, our study identifies EBF1 as an important determinant in regulating the balance of myeloid versus lymphoid potential in the earliest hematopoietic progenitors.

2022-06-30 | GSE189051 | GEO

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [ATAC-seq]

2022-06-30 | GSE189049 | GEO

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [Bulk RNA-seq]

2022-06-30 | GSE188884 | GEO

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [10x]

Project description:EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [10x]

| PRJNA781256 | ENA

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [ATAC-seq]

Project description:EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [ATAC-seq]

| PRJNA781258 | ENA

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [Bulk RNA-seq]

Project description:EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [Bulk RNA-seq]

| PRJNA780562 | ENA

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-30 | GSE189078 | GEO

A comprehensive Proteomic Investigation of Ebf1 Heterozygosity in pro-B lymphocytes utilizing Data Independent Acquisition

Project description:Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B-cell lineage development. Although studies have shown that Ebf1 haploinsufficiency is involved in the development of leukemia, no study has been conducted that characterizes the global effect of Ebf1 heterozygosity on the proteome of pro-B lymphocytes. Here, we employ both DIA (Data Independent Acquisition) and shotgun DDA (Data Dependent Acquisition) workflows for profiling proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells. Both DDA and DIA were able to reveal the downregulation of the EBF1 transcription factor in Ebf1+/- pro-B lymphocytes. Further examination of differentially expressed proteins by DIA revealed that, similar to EBF1, the expression of other B-cell lineage regulators, such as TCF3 and Pax5, is also down-regulated in Ebf1 heterozygous cells. Functional DIA analysis of differentially expressed proteins showed that EBF1 heterozygosity resulted in the deregulation of at least 8 transcription factors involved in lymphopoiesis, and to the deregulation of key proteins playing crucial roles in survival, development and differentiation of pro-B lymphocytes.

2017-12-20 | PXD008396 | Pride

Gene expression profile of EBF1-wt & EBF1-H240A

Project description:To study the function of EBF1-H240 residue, a gain-of function microarray analysis was performed by transducing Empty, Ebf1-wt and Ebf1-H240A expressing vectors into Ebf1-/- progenitor cells.

2016-11-21 | GSE87634 | GEO

Ebf1 ChIP

Project description:Ebf1 is a key determinant of B-lymphocyte specification. In order to identify unknown transcriptional targets, endogenous Ebf1 was isolated by chromatin-IP from primary pro-B cells and the copurified DNA was hybridized to promoter tiling arrays. Ebf1 was ChIPed using a polyclonal antibody directed against an N-terminal peptide from primary pro-B cells grown in the presence of Il7. The resulting DNA was analyzed by tiling array hybridization.

2010-06-24 | E-GEOD-21469 | biostudies-arrayexpress

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