title: Steady state peripheral blood provides cells with functional and metabolic characteristics of real hematopoietic stem cells.
abstract: Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood. However, no SP cells from SSBP have as yet been characterized. Here we showed that SP cells from SSPB exhibited a higher proliferative capacity and generated more clonogenic progenitors than non-SP cells in vitro. Furthermore, xenotransplantation studies on immunodeficient mice demonstrated that SP cells are up to 45 times more enriched in cells with engraftment capacity than non-SP cells. From a cell regulation point of view, we showed that SP activity depended on O2concentrations close to those found in HSC niches, an effect which is dependent on both hypoxia-induced factors HIF-1α and HIF-2α. Moreover SP cells displayed a reduced mitochondrial mass and, in particular, a lower mitochondrial activity compared to non-SP cells, while they exhibited a similar level of glucose incorporation. These results provided evidence that SP cells from SSPB displayed properties of very primitive cells and HSC, thus rendering them an interesting model for research and cell therapy.
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Bourdieu
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Avalon
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lapostolle
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.
authors.forename: Sadek
authors.initials: S
authors.lastname: Ismail
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Mombled
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Debeissat
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Guérinet
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Duchez
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Chevaleyre
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Marija
authors.initials: M
authors.lastname: Vlaski-Lafarge
authors.affiliation: INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Villacreces
authors.affiliation: INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Praloran
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Ivanovic
authors.affiliation: Etablissement Français du Sang-Aquitaine Limousin (EFS-AqLi), Bordeaux, France.|INSERM (U1035), Cellules souches hématopoïétiques normales et leucémiques, Bordeaux, France.|Univ. Bordeaux, Bordeaux, France.
authors.forename: Philippe
authors.identifier: http://orcid.org/0000-0001-5002-6012
authors.initials: P
authors.lastname: Brunet de la Grange
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism* / Q000637:transplantation; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D004734:Energy Metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005947:Glucose / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D058985:Side-Population Cells / Q000378:metabolism* / Q000637:transplantation; D014162:Transfection; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human
keywords: hematopoietic stem cells; metabolism; oxygen concentrations; peripheral blood; side population