| First Author | Knudsen KJ | Year | 2015 |
| Journal | Genes Dev | Volume | 29 |
| Issue | 18 | Pages | 1915-29 |
| PubMed ID | 26385962 | Mgi Jnum | J:331735 |
| Mgi Id | MGI:6868947 | Doi | 10.1101/gad.268409.115 |
| Citation | Knudsen KJ, et al. (2015) ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation. Genes Dev 29(18):1915-29 |
| abstractText | The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors that serve to restrict HSC differentiation. In the present work, we identify ETS (E-twenty-six)-related gene (ERG) as a critical factor protecting HSCs from differentiation. Specifically, loss of Erg accelerates HSC differentiation by >20-fold, thus leading to rapid depletion of immunophenotypic and functional HSCs. Molecularly, we could demonstrate that ERG, in addition to promoting the expression of HSC self-renewal genes, also represses a group of MYC targets, thereby explaining why Erg loss closely mimics Myc overexpression. Consistently, the BET domain inhibitor CPI-203, known to repress Myc expression, confers a partial phenotypic rescue. In summary, ERG plays a critical role in coordinating the balance between self-renewal and differentiation of HSCs. |
