Hypoxic induction of vascular endothelial growth factor regulates erythropoiesis but not hematopoietic stem cell function in the fetal liver

TY - JOUR

T1 - Hypoxic induction of vascular endothelial growth factor regulates erythropoiesis but not hematopoietic stem cell function in the fetal liver

AU - Rehn, Matilda

AU - Kertész, Zsuzsanna

AU - Cammenga, Jörg

N1 - Copyright © 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Hypoxia is an important factor in the hematopoietic stem cell (HSC) niche in the bone marrow, but whether it also plays a role in the regulation of fetal liver (FL) HSCs is unclear. Vascular endothelial growth factor A (VEGFA) is essential for adult HSC survival, and hypoxic induction of VEGFA in adult HSCs is required for proper function. Loss of hypoxia-regulated VEGFA expression increases the number of phenotypically defined hematopoietic stem and progenitor cells in the FL, but whether stem cell function is affected in FL HSCs has not, to our knowledge, been assessed. We show that fetal erythropoiesis is severely impaired when hypoxic induction of VEGFA is lacking. FL HSCs deficient for hypoxia-induced VEGFA expression have normal HSC function, arguing against a hypoxic FL HSC niche. However, after adaptation of FL HSCs to the bone marrow microenvironment, FL HSCs lose their function, as measured by serial transplantation.

AB - Hypoxia is an important factor in the hematopoietic stem cell (HSC) niche in the bone marrow, but whether it also plays a role in the regulation of fetal liver (FL) HSCs is unclear. Vascular endothelial growth factor A (VEGFA) is essential for adult HSC survival, and hypoxic induction of VEGFA in adult HSCs is required for proper function. Loss of hypoxia-regulated VEGFA expression increases the number of phenotypically defined hematopoietic stem and progenitor cells in the FL, but whether stem cell function is affected in FL HSCs has not, to our knowledge, been assessed. We show that fetal erythropoiesis is severely impaired when hypoxic induction of VEGFA is lacking. FL HSCs deficient for hypoxia-induced VEGFA expression have normal HSC function, arguing against a hypoxic FL HSC niche. However, after adaptation of FL HSCs to the bone marrow microenvironment, FL HSCs lose their function, as measured by serial transplantation.

KW - Animals

KW - Bone Marrow/metabolism

KW - Bone Marrow Transplantation

KW - Cell Survival

KW - Erythropoiesis/genetics

KW - Fetus

KW - Gene Expression

KW - Hematopoietic Stem Cells/metabolism

KW - Hypoxia/genetics

KW - Liver/metabolism

KW - Mice

KW - Mice, Knockout

KW - Stem Cell Niche

KW - Vascular Endothelial Growth Factor A/genetics

U2 - 10.1016/j.exphem.2014.08.002

DO - 10.1016/j.exphem.2014.08.002

M3 - Journal article

C2 - 25220588

SN - 0301-472X

VL - 42

SP - 941-4.e1

JO - Experimental Hematology

JF - Experimental Hematology

IS - 11

ER -