01 December 2015
Propagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture
Fridriksdottir, Agla J., Jiyoung Kim, Rene Villadsen, Marie Christine Klitgaard, Branden M. Hopkinson, Ole William Petersen & Lone Ronnov-Jessen (2015). Propagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture. Nature Communications, 6, doi:10.1038/ncomms9786.
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.