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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2003-02-0448.
Submitted February 10, 2003
Accepted April 22, 2003
The HIF family member EPAS1/HIF-2 is required for normal hematopoiesis in mice
Marzia Scortegagna, Margaret A Morris, Yavuz Oktay, Michael Bennett, and Joseph A Garcia*
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
* Corresponding author; email: joseph.garcia{at}utsouthwestern.edu.
Hypoxic stress plays a role in pathophysiologic states such as myocardial infarction and cerebral vascular events as well as in normal physiologic conditions including development and hematopoiesis. Members of the hypoxia induced factor (HIF) family function as transcriptional regulators of genes involved in the hypoxic response. After generating adult mice that globally lack EPAS1 (EPAS1, also known as HIF-2 /HRF/HLF/MOP3), the second member of the HIF family, characterization of the hematopoietic cell population indicated that the loss of EPAS1/HIF-2 resulted in pancytopenia. Using bone marrow reconstitution experiments of lethal-irradiated hosts, we have defined the extent and site of hematopoietic impairment in the EPAS1/HIF-2 null mice. These data suggest a critical role for EPAS1/HIF-2 in maintaining a functional microenvironment in the bone marrow for effective hematopoiesis.
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