ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

作者：Knudsen Kasper Jermiin; Rehn Matilda; Hasemann Marie Sigurd; Rapin Nicolas; Bagger Frederik Otzen; Ohlsson Ewa; Willer Anton; Frank Anne Katrine; Sondergaard Elisabeth; Jendholm Johan; Thoren Lina; Lee Julie; Rak Justyna; Theilgaard Monch Kim; Porse Bo Torben^*

来源：Genes & Development, 2015, 29(18): 1915-1929.

DOI：10.1101/gad.268409.115

• hematopoietic stem cell
• ERG
• MYC
• differentiation
• self-renewal
• CPI-203

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.

• 出版日期2015-9-15