ETV2/ER71 regulates hematopoietic regeneration by promoting hematopoietic stem cell proliferation
Year: 2017
Type: article
Abstract: 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 (Etv2; also known as Er71) 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 c-Kit to be downstream of ETV2. As such, lentiviral c-Kit expression rescued Etv2-deficient HSPC proliferation defects in vitro and in short-term BM transplantation in vivo. These findings demonstrate that Etv2 is an important regulator of hematopoietic regeneration.
DOI: 10.1084/jem.20160923
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1384347966, G1661872581, G1867112536, G200058312, G26147564, G3378495485, Connecting transposable elements and regulatory innovation using ENCODE data, G5740585382, The WashU 4DN Network Data Coordination and Integration Center, G9000008527, G9000018247, G9000070636, G9000077927, G9000139397, G9000226449, TRAINING IN THE IMMUNOBIOLOGY AND MOLECULAR CELL BIOLOGY OF CANCER, G953418112
OpenAlex ID: W2611714062