Transcriptomics

Dataset Information

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HIF knockdowns in human hematopoietic stem cells


ABSTRACT: Hematopoietic stem cells (HSCs), which reside in bone marrow niches, are exposed to low levels of oxygen and follow an oxygen gradient throughout their differentiation. Hypoxia-inducible factors (HIFs) are the main factors regulating the cell response to oxygen variation. Recent studies using conditional knockout mouse models have unveiled a major role of HIF-1a in the maintenance of murine HSCs, however the role of HIF-2a is still unclear. Here, we show that knockdown of HIF-2a and to a much lower extent, HIF-1a impedes the long-term repopulating ability of human CD34+ umbilical cord blood derived cells. The defects observed in hematopoietic stem and progenitor cell (HSPC) function after HIF-2a knockdown was due to an increase in the production of reactive oxygen species (ROS), which increases the endoplasmic reticulum (ER) stress in HSPCs and triggers apoptosis by the activation of the unfolded-protein-response (UPR) pathway. Importantly, HIF-2a deregulation also resulted in a significant decrease of engraftment of human acute myeloid leukemia (AML) cells. Overall, our data demonstrates a key role of HIF-2a in the maintenance of human HSPCs and in the survival of primary AML cells. 2 controls and 2 shHIF2 CD34+ cell samples sorted from mice after 6 weeks of engraftment

ORGANISM(S): Homo sapiens  

SUBMITTER: Frédéric Mazurier   Martin Serrano-Sanchez  Hubert de Verneuil  Dominique Bonnet  John Gribben  Fernando Anjos-Afonso  Hamid R Rezvani  Katie Foster  Kevin Rouault-Pierre  Richard James Mitter  Lourdes Lopez-Onieva  Zoran Ivanovic  David Taussig  Mitter Richard  Isabelle Lamrissi-Garcia 

PROVIDER: E-GEOD-49897 | ArrayExpress | 2014-01-01

SECONDARY ACCESSION(S): GSE49897PRJNA215276

REPOSITORIES: GEO, ArrayExpress

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