Title |
The aryl hydrocarbon receptor nuclear translocator is an essential regulator of murine hematopoietic stem cell viability
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Published in |
Blood, April 2015
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DOI | 10.1182/blood-2014-10-607267 |
Pubmed ID | |
Authors |
Bryan L Krock, Tzipora S Eisinger-Mathason, Dionysios N Giannoukos, Jessica E Shay, Mercy Gohil, David S Lee, Michael S Nakazawa, Julie Sesen, Nicolas Skuli, M Celeste Simon |
Abstract |
Hypoxia Inducible Factors (HIFs) are master regulators of the transcriptional response to low oxygen and play essential roles in embryonic development, tissue homeostasis and disease. Recent studies have demonstrated that hematopoietic stem cells (HSCs) within the bone marrow localize to a hypoxic niche and that HIF-1α promotes HSC adaptation to stress. As the related factor HIF-2α is also expressed in HSCs, the combined role of HIF-1α and HIF-2α in HSC maintenance is unclear. To this end, we have conditionally deleted the HIF-α dimerization partner, the Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) in the hematopoietic system to ablate activity of both HIF-1α and HIF-2α and assessed the functional consequence of ARNT deficiency on fetal liver and adult hematopoiesis. We determined that ARNT is essential for adult and fetal HSC viability and homeostasis. Importantly, conditional knockout of both Hif-1α and Hif-2α phenocopied key aspects of these HSC phenotypes, demonstrating that the impact of Arnt deletion is primarily HIF dependent. ARNT-deficient long term HSCs underwent apoptosis, potentially due to reduced BCL-2 and VEGF-A expression. Our results suggest that HIF activity may regulate HSC homeostasis through these pro-survival factors. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 3% |
Germany | 1 | 2% |
Unknown | 55 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 11 | 19% |
Student > Ph. D. Student | 10 | 17% |
Student > Master | 9 | 16% |
Student > Bachelor | 5 | 9% |
Student > Doctoral Student | 4 | 7% |
Other | 8 | 14% |
Unknown | 11 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 20 | 34% |
Agricultural and Biological Sciences | 17 | 29% |
Medicine and Dentistry | 6 | 10% |
Nursing and Health Professions | 1 | 2% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
Other | 2 | 3% |
Unknown | 11 | 19% |