ETV2/ER71 regulates hematopoietic regeneration by promoting hematopoietic stem cell proliferation.

Recent studies have established that hematopoietic stem cells (HSCs) are quiescent in homeostatic conditions but undergo extensive cell cycle and expansion upon bone marrow (BM) transplantation or hematopoietic injury. The molecular basis for HSC activation and expansion is not completely understood. In this study, we found that key developmentally critical genes controlling hematopoietic stem and progenitor cell (HSPC) generation were up-regulated in HSPCs upon hematopoietic injury. In particular, we found that the ETS transcription factor Ets variant 2 (; also known as ) was up-regulated by reactive oxygen species in HSPCs and was necessary in a cell-autonomous manner for HSPC expansion and regeneration after BM transplantation and hematopoietic injury. We found to be downstream of ETV2. As such, lentiviral expression rescued -deficient HSPC proliferation defects in vitro and in short-term BM transplantation in vivo. These findings demonstrate that is an important regulator of hematopoietic regeneration.