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J Exp Med. 2017 Jun 5;214(6):1643-1653. doi: 10.1084/jem.20160923. Epub 2017 May 1.

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

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
2
The People's Hospital of Hunan Province and Hunan Normal University Institute for Clinical and Translational Science, Changsha, Hunan 410006, China.
3
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110.
4
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 kchoi@wustl.edu.
5
Developmental, Regenerative, and Stem Cell Biology Program, Washington University School of Medicine, St. Louis, MO 63110.

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.

PMID:
28461595
PMCID:
PMC5460995
DOI:
10.1084/jem.20160923
[Indexed for MEDLINE]
Free PMC Article

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