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

Guitart, A.V. et al. (2013) Hif-2 is not essential for cell-autonomous hematopoietic stem cell maintenance. Blood, 122(10), pp. 1741-1745. (doi: 10.1182/blood-2013-02-484923)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gezer, Dr Deniz and Subramani, Miss Chithra and Armesilla-Diaz, Dr Alejandro and Holyoake, Professor Tessa and Dunn, Mrs Karen and Vukovic, Ms Milica and Guitart, Dr Amelie and Kranc, Professor Kamil
• Authors: Guitart, A.V., Subramani, C., Armesilla-Diaz, A., Smith, G., Sepulveda, C., Gezer, D., Vukovic, M., Dunn, K., Pollard, P., Holyoake, T.L., Enver, T., Ratcliffe, P.J., and Kranc, K.R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Blood
• Publisher: American Society of Hematology
• ISSN: 0006-4971
• ISSN (Online): 1528-0020