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

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

PROVIDER: PRJNA525888 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8691610_1.fastq.gz	Fastqsanger.gz
	SRR8691610_2.fastq.gz	Fastqsanger.gz
	SRR8691620_1.fastq.gz	Fastqsanger.gz
	SRR8691620_2.fastq.gz	Fastqsanger.gz
	SRR8691611_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:Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem and cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Ebf1-deficient 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 decreased the numbers of HSPCs and myeloid cells. EBF1 in the bone marrow niche regulates a transcriptional program that determines the functional interactions with HSCs and the long-term balance between the myeloid and lymphoid cell fates.

2020-03-01 | GSE127970 | GEO

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

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.

2020-02-17 | GSE128089 | GEO

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

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

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Longâterm engraftment of primary bone marrow stroma promotes hematopoietic reconstitution after transplantation

Project description:Restoration of hematopoiesis upon bone marrow (BM) transplantation relies on the engraftment, expansion and function of transplanted hematopoietic stem cells (HSC). However, the number of donorâderived HSC typically remain much below that present in normal individuals and this likely limits and delays hematopoietic recovery. HSC depend on supportive stromal niches, however, whether the preâconditioning required for BM transplantation damages this stromal niche has not been evaluated extensively. Using mouse models, we now find that that BM stroma cells (BMSC) are severely and permanently damaged by preâconditioning. Transplantation of primary but not cultured BMSC quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent CD73+ CD105â Sca1+ BMSC subpopulation. BMSC coâtransplantation significantly ameliorates clinical side effects of BM transplantation and doubles expansion of functional, donorâ derived HSC, demonstrating the potential of stroma transplantation to improve HSC transplantation. Purified CD45âTer119âCD73+ CD105â and CD45âTer119âCD73+ CD105+ cells were directly sorted on lysis buffer with FACS Aria 2 in triplicate.

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Stromal Repair via Long-term Engraftment of Primary Bone Marrow Stroma Improves Hematopoietic Stem Cell Transplantation

Project description:Stromal Repair via Long-term Engraftment of Primary Bone Marrow Stroma Improves Hematopoietic Stem Cell Transplantation

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Expression data from long-term Ebf1-deficient, CD19+, Bcl2tg cells

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Expression data from long-term Ebf1-deficient, CD19+, Bcl2tg cells

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