title: Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance.
abstract: Local hypoxia in hematopoietic stem cell (HSC) niches is thought to regulate HSC functions. Hypoxia-inducible factor-1 (Hif-1) and Hif-2 are key mediators of cellular responses to hypoxia. Although oxygen-regulated α-subunits of Hifs, namely Hif-1α and Hif-2α, are closely related, they play overlapping and also distinct functions in nonhematopoietic tissues. Although Hif-1α-deficient HSCs lose their activity on serial transplantation, the role for Hif-2α in cell-autonomous HSC maintenance remains unknown. Here, we demonstrate that constitutive or inducible hematopoiesis-specific Hif-2α deletion does not affect HSC numbers and steady-state hematopoiesis. Furthermore, using serial transplantations and 5-fluorouracil treatment, we demonstrate that HSCs do not require Hif-2α to self-renew and recover after hematopoietic injury. Finally, we show that Hif-1α deletion has no major impact on steady-state maintenance of Hif-2α-deficient HSCs and their ability to repopulate primary recipients, indicating that Hif-1α expression does not account for normal behavior of Hif-2α-deficient HSCs.
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Amelie V
authors.initials: AV
authors.lastname: Guitart
authors.forename: Chithra
authors.initials: C
authors.lastname: Subramani
authors.forename: Alejandro
authors.initials: A
authors.lastname: Armesilla-Diaz
authors.forename: Gillian
authors.initials: G
authors.lastname: Smith
authors.forename: Catarina
authors.initials: C
authors.lastname: Sepulveda
authors.forename: Deniz
authors.initials: D
authors.lastname: Gezer
authors.forename: Milica
authors.initials: M
authors.lastname: Vukovic
authors.forename: Karen
authors.initials: K
authors.lastname: Dunn
authors.forename: Patrick
authors.initials: P
authors.lastname: Pollard
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
authors.forename: Tariq
authors.initials: T
authors.lastname: Enver
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ratcliffe
authors.forename: Kamil R
authors.initials: KR
authors.lastname: Kranc
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D017353:Gene Deletion; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1