The HIF family member EPAS1/HIF-2alpha is required for normal hematopoiesis in mice.
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 inducible factor (HIF) family function as transcriptional regulators of genes involved in the hypoxic response. After generating adult mice that globally lack endothelial PAS domain protein 1 (EPAS1, also known as HIF-2alpha/HRF/HLF/MOP3), the second member of the HIF family, characterization of the hematopoietic cell population indicated that the loss of EPAS1/HIF-2alpha resulted in pancytopenia. Using bone marrow reconstitution experiments of lethally irradiated hosts, we have defined the extent and site of hematopoietic impairment in the EPAS1/HIF-2alpha null mice. These data suggest a critical role for EPAS1/HIF-2alpha in maintaining a functional microenvironment in the bone marrow for effective hematopoiesis.
University of Texas Southwestern Medical Center, Department of Internal Medicine, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Marzia
M
Scortegagna
Margaret A
MA
Morris
Yavuz
Y
Oktay
Michael
M
Bennett
Joseph A
JA
Garcia
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001853:Bone Marrow / Q000502:physiology; D016026:Bone Marrow Transplantation; D005434:Flow Cytometry; D006400:Hematocrit; D006410:Hematopoiesis / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D015534:Trans-Activators; D000099162:Endothelial PAS Domain-Containing Protein 1