期刊
BLOOD
卷 122, 期 10, 页码 1741-1745出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-02-484923
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资金
- Cancer Research UK [C29967/A14633, A11008]
- Leukaemia & Lymphoma Research [08037, 10030, 11047, 11041]
- Kay Kendall Leukaemia Fund [KKL506]
- Royal Society [2010R1]
- National Health Service Greater Glasgow
- Clyde Endowment Fund
- MRC [MC_U137973817] Funding Source: UKRI
- Cancer Research UK [12796, 14633] Funding Source: researchfish
- Medical Research Council [MR/K017047/1B, MC_U137973817] Funding Source: researchfish
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 alpha-subunits of Hifs, namely Hif-1 alpha and Hif-2 alpha, are closely related, they play overlapping and also distinct functions in nonhematopoietic tissues. Although Hif-1 alpha-deficient HSCs lose their activity on serial transplantation, the role for Hif-2 alpha in cell-autonomous HSC maintenance remains unknown. Here, we demonstrate that constitutive or inducible hematopoiesis-specific Hif-2 alpha 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-2 alpha to self-renew and recover after hematopoietic injury. Finally, we show that Hif-1 alpha deletion has no major impact on steady-state maintenance of Hif-2 alpha-deficient HSCs and their ability to repopulate primary recipients, indicating that Hif-1 alpha expression does not account for normal behavior of Hif-2 alpha-deficient HSCs.
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