| First Author | Vukovic M | Year | 2016 |
| Journal | Blood | Volume | 127 |
| Issue | 23 | Pages | 2841-6 |
| PubMed ID | 27060169 | Mgi Jnum | J:234801 |
| Mgi Id | MGI:5790896 | Doi | 10.1182/blood-2015-10-677138 |
| Citation | Vukovic M, et al. (2016) Adult hematopoietic stem cells lacking Hif-1alpha self-renew normally. Blood 127(23):2841-6 |
| abstractText | The hematopoietic stem cell (HSC) pool is maintained under hypoxic conditions within the bone marrow microenvironment. Cellular responses to hypoxia are largely mediated by the hypoxia-inducible factors, Hif-1 and Hif-2. The oxygen-regulated alpha subunits of Hif-1 and Hif-2 (namely, Hif-1alpha and Hif-2alpha) form dimers with their stably expressed beta subunits and control the transcription of downstream hypoxia-responsive genes to facilitate adaptation to low oxygen tension. An initial study concluded that Hif-1alpha is essential for HSC maintenance, whereby Hif-1alpha-deficient HSCs lost their ability to self-renew in serial transplantation assays. In another study, we demonstrated that Hif-2alpha is dispensable for cell-autonomous HSC maintenance, both under steady-state conditions and following transplantation. Given these unexpected findings, we set out to revisit the role of Hif-1alpha in cell-autonomous HSC functions. Here we demonstrate that inducible acute deletion of Hif-1alpha has no impact on HSC survival. Notably, unstressed HSCs lacking Hif-1alpha efficiently self-renew and sustain long-term multilineage hematopoiesis upon serial transplantation. Finally, Hif-1alpha-deficient HSCs recover normally after hematopoietic injury induced by serial administration of 5-fluorouracil. We therefore conclude that despite the hypoxic nature of the bone marrow microenvironment, Hif-1alpha is dispensable for cell-autonomous HSC maintenance. |
