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

Amelie Guitart, Chithra Subramani, Alejandro Armesilla-Diaz, Gillian Smith, Catarina Sepulveda, Deniz Gezer, Milica Vukovic, Karen Dunn, Patrick Pollard, Tessa L Holyoake, Tariq Enver, Peter J Ratcliffe, Kamil R Kranc

Research output: Contribution to journalArticlepeer-review


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-1α and Hif-2α, are closely related, they play overlapping and also distinct functions in non-hematopoietic tissues. While Hif-1α-deficient HSCs lose their activity upon 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-FU treatment we demonstrate that HSCs do not require Hif-2α to self-renew and recover following 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.
Original languageEnglish
Pages (from-to)1741-1745
Issue number10
Publication statusPublished - Sep 2013


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