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

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

PROVIDER: PRJNA526435 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8707280_1.fastq.gz	Fastqsanger.gz
	SRR8707280_2.fastq.gz	Fastqsanger.gz
	SRR8707290_1.fastq.gz	Fastqsanger.gz
	SRR8707290_2.fastq.gz	Fastqsanger.gz
	SRR8707300_1.fastq.gz	Fastqsanger.gz

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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

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

| PRJNA525888 | ENA

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

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.

2020-03-01 | GSE128743 | GEO

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.

2016-09-01 | E-GEOD-79091 | biostudies-arrayexpress

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

| PRJNA528662 | ENA

Notch Activation Confers Enhanced Lymphoid Potential in Murine ESC/iPSC-derived HSC and Reconstitutes Adaptive Immunity In Vivo [Microarray expression]

Project description:Hematopoietic stem cell (HSC) transplantation has the potential to cure blood disorders but is limited by donor availability. Hence innovative approaches to engineer HSC are critically needed. HoxB4 over-expression in mouse embryonic stem cell-derived HSC (ESC-HSC) confers long-term engraftment, yet lacks efficient lymphogenesis. Transcriptome comparison of ESC-HSC versus embryo-derived HSC showed that ESC-HSC are deficient in expression programs activated by Notch. Therefore, we aim to improve ESC-HSC by further providing Notch signals through Notch1 intra-cellular domain transgene activation or by ligand stimulation. Here, we report that Notch-enhanced ESC-HSC (nESC-HSC) confer clonal multipotentiality with robust lymphopoiesis that endows adaptive immunity. Notably, nESC-HSC further evolve to a hybrid cell-type co-expressing gene regulatory networks of hematopoietic stem/progenitor cells and differentiated lineages at single-cell level that accounts for multipotentiality. Our work reveals a proof-of-concept model of HSC engineering by assembling self-renewing factor and lineage-guiding pathway into one product-cell that functionally recapitulate HSC in vivo.

2016-12-21 | GSE71793 | GEO

Notch Activation Confers Enhanced Lymphoid Potential in Murine ESC/iPSC-derived HSC and Reconstitutes Adaptive Immunity In Vivo [RNA-Seq]

2016-12-21 | GSE71794 | GEO

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

Project description:An assessment of a role of Ebf1 in committed B lineage cells. In this study, we adopted the strategy of deleting Ebf1 after reconstitution of Rag2-/-Il2rg-/- mice and found that committed pre-B cells could be converted into T cells and ILCs upon deletion of Ebf1. We used µ-arrays to gain insight into changes in gene expression of CD19+ Ebf1-deficient cells. The dataset was compared with microarray data available for different hematopoietic developmental stages (GSE15907). The complete dataset is linked below as a supplementary file.

2013-06-01 | E-GEOD-46349 | biostudies-arrayexpress

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

2013-06-01 | GSE46349 | GEO