@misc{10481/98868,
year = {2013},
month = {11},
url = {https://hdl.handle.net/10481/98868},
abstract = {Hematopoietic stem and progenitor cells (HSPCs) are exposed to low levels of oxygen in the bone marrow niche, and hypoxia-inducible factors (HIFs) are the main regulators of cellular responses to oxygen variation. Recent studies using conditional knockout mouse models have unveiled a major role for HIF-1α in the maintenance of murine HSCs; however, the role of HIF-2α is still unclear. Here, we show that knockdown of HIF-2α, and to a much lesser extent HIF-1α, impedes the long-term repopulating ability of human CD34(+) umbilical cord blood cells. HIF-2α-deficient HSPCs display increased production of reactive oxygen species (ROS), which subsequently stimulates endoplasmic reticulum (ER) stress and triggers apoptosis by activation of the unfolded-protein-response (UPR) pathway. HIF-2α deregulation also significantly decreased engraftment ability of human acute myeloid leukemia (AML) cells. Overall, our data demonstrate a key role for HIF-2α in the maintenance of human HSPCs and in the survival of primary AML cells.},
title = {HIF-2α protects human hematopoietic stem/progenitors and acute myeloid leukemic cells from apoptosis induced by endoplasmic reticulum stress},
doi = {10.1016/j.stem.2013.08.011},
author = {Rouault-Pierre, Kevin and López Onieva, Lourdes and Foster, Katie and Anjos-Afonso, Fernando and Lamrissi-Garcia, Isabelle and Serrano-Sanchez, Martin and Mitter, Richard and Ivanovic, Zoran and de Verneuil, Hubert and Gribben, John and Taussig, David and Reza Rezvani, Hamid and Mazurier, Frédéric and Bonnet, Dominique},
}