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EBF-1 mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential

ABSTRACT: EBF-1 mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential

PROVIDER: PRJNA528662 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8776170_1.fastq.gz	Fastqsanger.gz
	SRR8776170_2.fastq.gz	Fastqsanger.gz
	SRR8776180_1.fastq.gz	Fastqsanger.gz
	SRR8776180_2.fastq.gz	Fastqsanger.gz
	SRR8776190_1.fastq.gz	Fastqsanger.gz

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EBF1-mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential

Project description:EBF1-mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential

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EBF1-mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential [HSC]

Project description:EBF1-mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential [HSC]

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EBF1-mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential

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Project description:Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem and cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Here, we investigate the role of Early B-cell factor 1 (EBF1) in MSCs to support hematopoiesis. Ebf1-/- MSCs have reduced mesenchymal lineage potential. Ebf1 deletion in Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+CD45-CD31-Lin- (PαS) cells in the bone marrow decreases the numbers of HSPCs and myeloid cells. Single cell and bulk transcriptome analysis, combined with analysis of chromatin accessibility in EBF1-deficient MSCs revealed an altered niche composition and MSCs identity. In HSCs that were exposed to the EBF1-deficient niche, we detected an altered chromatin accessibility and impaired occupancy by AP-1, ETS and IRF proteins. Notably, the effects of the EBF1-deficient niche on HSPCs are retained after transfer to a wild-type niche. Thus, genetic alterations in the bone marrow niche can result in long-term changes of the chromatin landscape in HSCs.

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EBF-1 mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential

Project description:Here, we investigate the role of Early B-cell factor 1 (EBF1) in MSCs to support hematopoiesis. Ebf1 deletion in Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+CD45-CD31-Lin- (PαS) cells in the bone marrow decreases the numbers of HSCs and myeloid cells. Single cell and bulk transcriptome analysis, combined with analysis of chromatin accessibility in EBF1-deficient MSCs revealed decreased expression of adhesion molecules and altered niche composition. In consequence, HSCs exposed to the EBF1-deficient niche, exhibit altered chromatin accessibility and impaired occupancy by myeloid regulators like AP-1, ETS and IRF.

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