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Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance.

TitleHif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance.
Publication TypeJournal Article
Year of Publication2013
AuthorsGuitart A, Subramani C, Armesilla-Diaz A, Smith G, Sepulveda C, Gezer D, Vukovic M, Dunn K, Pollard P, Holyoake TL, Enver T, Ratcliffe PJ, Kranc KR
Date Published2013 Sep 5
KeywordsAnimals, Basic Helix-Loop-Helix Transcription Factors, Cell Proliferation, Cell Survival, Female, Gene Deletion, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Male, Mice

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.

Alternate JournalBlood
PubMed ID23894152
Grant ListA11008 / / Cancer Research UK / United Kingdom
C29967/A14633 / / Cancer Research UK / United Kingdom
MC_U137973817 / / Medical Research Council / United Kingdom