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

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. Single cells from the bone marrow stroma as well as hematopoietic progenitors were sorted into 384-well plates and processed using a modified version of the CEL-Seq2 protocol (Hasimshony et al. 2016, Genome Biology, DOI: 10.1186/s13059-016-0938-8).