title: Hypoxic induction of vascular endothelial growth factor regulates erythropoiesis but not hematopoietic stem cell function in the fetal liver.
abstract: 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.
authors.affiliation: Division of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Matilda
authors.initials: M
authors.lastname: Rehn
authors.affiliation: Division of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kertész
authors.affiliation: Division of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Department of Hematology, Skåne University Hospital, Lund, Sweden. Electronic address: jorg.cammenga@med.lu.se.
authors.forename: Jörg
authors.initials: J
authors.lastname: Cammenga
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D004920:Erythropoiesis / Q000235:genetics*; D005333:Fetus; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055153:Stem Cell Niche; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse