| First Author | Guitart AV | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 10 | Pages | 1741-5 |
| PubMed ID | 23894152 | Mgi Jnum | J:202361 |
| Mgi Id | MGI:5518525 | Doi | 10.1182/blood-2013-02-484923 |
| Citation | Guitart AV, et al. (2013) Hif-2alpha is not essential for cell-autonomous hematopoietic stem cell maintenance. Blood 122(10):1741-5 |
| abstractText | 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-1alpha and Hif-2alpha, are closely related, they play overlapping and also distinct functions in nonhematopoietic tissues. Although Hif-1alpha-deficient HSCs lose their activity on serial transplantation, the role for Hif-2alpha in cell-autonomous HSC maintenance remains unknown. Here, we demonstrate that constitutive or inducible hematopoiesis-specific Hif-2alpha 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-2alpha to self-renew and recover after hematopoietic injury. Finally, we show that Hif-1alpha deletion has no major impact on steady-state maintenance of Hif-2alpha-deficient HSCs and their ability to repopulate primary recipients, indicating that Hif-1alpha expression does not account for normal behavior of Hif-2alpha-deficient HSCs. |
