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| Status |
Public on Feb 17, 2020 |
| Title |
EBF1-mutant bone marrow stroma confers long-term changes in hematopoietic stem cell potential [HSC] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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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| Overall design |
RNA-Seq analysis of endogenous, primary transplanted Ebf+/+ PrxCre and Ebffl/fl PrxCre LT HSCs; ATAC-Seq analysis of endogenous, primary and secondary transplanted Ebf+/+ PrxCre and Ebffl/fl PrxCre LT HSCs.
Please note that the processed data generated from multiple samples is linked to the corresponding rep1 sample records or to the Series records.
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| Contributor(s) |
Marta D, Cauchy P, Grosschedl R |
| Citation(s) |
32066955 |
| |
| Submission date |
Mar 11, 2019 |
| Last update date |
Feb 28, 2020 |
| Contact name |
Pierre Daniel Cauchy |
| E-mail(s) |
cauchy@ie-freiburg.mpg.de
|
| Phone |
+49 (0)761 270-77576
|
| Organization name |
University Medical Center Freiburg
|
| Department |
Zentrum für Translationale Zellforschung
|
| Lab |
AG Onco-Immunology
|
| Street address |
Breisacher Str. 115
|
| City |
Freiburg |
| State/province |
Baden-Württemberg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
| |
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| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA526435 |
| SRA |
SRP188075 |
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