Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance.
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 overlapp...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797083743399182336 |
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| author | Guitart, A Subramani, C Armesilla-Diaz, A Smith, G Sepulveda, C Gezer, D Vukovic, M Dunn, K Pollard, P Holyoake, T Enver, T Ratcliffe, P Kranc, K |
| author_facet | Guitart, A Subramani, C Armesilla-Diaz, A Smith, G Sepulveda, C Gezer, D Vukovic, M Dunn, K Pollard, P Holyoake, T Enver, T Ratcliffe, P Kranc, K |
| author_sort | Guitart, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:45:46Z |
| format | Journal article |
| id | oxford-uuid:985ea4bf-8b2d-4577-8d50-abf01319f31f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:45:46Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:985ea4bf-8b2d-4577-8d50-abf01319f31f2022-03-27T00:06:26ZHif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:985ea4bf-8b2d-4577-8d50-abf01319f31fEnglishSymplectic Elements at Oxford2013Guitart, ASubramani, CArmesilla-Diaz, ASmith, GSepulveda, CGezer, DVukovic, MDunn, KPollard, PHolyoake, TEnver, TRatcliffe, PKranc, KLocal 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. |
| spellingShingle | Guitart, A Subramani, C Armesilla-Diaz, A Smith, G Sepulveda, C Gezer, D Vukovic, M Dunn, K Pollard, P Holyoake, T Enver, T Ratcliffe, P Kranc, K Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance. |
| title | Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance. |
| title_full | Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance. |
| title_fullStr | Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance. |
| title_full_unstemmed | Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance. |
| title_short | Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance. |
| title_sort | hif 2α is not essential for cell autonomous hematopoietic stem cell maintenance |
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