| First Author | Lenaerts A | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 11 | PubMed ID | 36048017 |
| Mgi Jnum | J:330859 | Mgi Id | MGI:7343526 |
| Doi | 10.1084/jem.20212437 | Citation | Lenaerts A, et al. (2022) EBF1 primes B-lymphoid enhancers and limits the myeloid bias in murine multipotent progenitors. J Exp Med 219(11):e20212437 |
| abstractText | Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) generate all cells of the blood system. Despite their multipotency, MPPs display poorly understood lineage bias. Here, we examine whether lineage-specifying transcription factors, such as the B-lineage determinant EBF1, regulate lineage preference in early progenitors. We detect low-level EBF1 expression in myeloid-biased MPP3 and lymphoid-biased MPP4 cells, coinciding with expression of the myeloid determinant C/EBPalpha. Hematopoietic deletion of Ebf1 results in enhanced myelopoiesis and reduced HSC repopulation capacity. Ebf1-deficient MPP3 and MPP4 cells exhibit an augmented myeloid differentiation potential and a transcriptome with an enriched C/EBPalpha signature. Correspondingly, EBF1 binds the Cebpa enhancer, and the deficiency and overexpression of Ebf1 in MPP3 and MPP4 cells lead to an up- and downregulation of Cebpa expression, respectively. In addition, EBF1 primes the chromatin of B-lymphoid enhancers specifically in MPP3 cells. Thus, our study implicates EBF1 in regulating myeloid/lymphoid fate bias in MPPs by constraining C/EBPalpha-driven myelopoiesis and priming the B-lymphoid fate. |
