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

Journal article

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: Guitart, A; Subramani, C; Armesilla-Diaz, A; Smith, G; Sepulveda, C

• Publication status: Published
• Journal: Blood
• Volume: 122
• Issue: 10
• Pages: 1741-1745
• Publication date: 2013-09-01
• DOI: 10.1182/blood-2013-02-484923
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Animals; Hematopoietic Stem Cell Transplantation; Gene Deletion; Cell Survival; Female; Male; Hematopoietic Stem Cells; Hematopoiesis; Basic Helix-Loop-Helix Transcription Factors; Mice; Cell Proliferation