Uta Rabenhorst, Frederic Bastian Thalheimer, Katharina Gerlach, Marek Kijonka, Stefanie Böhm, Daniela Sandra Krause, Franz Vauti, Hans-Henning Arnold, Timm Schroeder, Frank Schnütgen, Harald von Melchner, Michael A. Rieger, Martin Zörnig
- The ability of hematopoietic stem cells (HSCs) to self-renew is a prerequisite for the establishment of definitive hematopoiesis and life-long blood regeneration. Here, we report the single-stranded DNA-binding transcriptional regulator far upstream element (FUSE)-binding protein 1 (FUBP1) as an essential factor of HSC self-renewal. Functional inactivation of FUBP1 in two different mouse models resulted in embryonic lethal anemia at around E15.5 caused by severely diminished HSCs. Fetal and adult HSCs lacking FUBP1 revealed an HSC-intrinsic defect in their maintenance, expansion, and long-term blood reconstitution, but could differentiate into all hematopoietic lineages. FUBP1-deficient adult HSCs exhibit significant transcriptional changes, including upregulation of the cell-cycle inhibitor p21 and the pro-apoptotic Noxa molecule. These changes caused an increase in generation time and death of HSCs as determined by video-microscopy-based tracking. Our data establish FUBP1 and its recognition of single-stranded genomic DNA as an important element in the transcriptional regulation of HSC self-renewal.
MetadatenAuthor: | Uta Rabenhorst, Frederic Bastian ThalheimerORCiDGND, Katharina Gerlach, Marek Kijonka, Stefanie BöhmORCiD, Daniela Sandra KrauseORCiDGND, Franz Vauti, Hans-Henning Arnold, Timm Schroeder, Frank SchnütgenORCiDGND, Harald von Melchner, Michael A. RiegerORCiDGND, Martin ZörnigORCiD |
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URN: | urn:nbn:de:hebis:30:3-417977 |
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DOI: | https://doi.org/10.1016/j.celrep.2015.05.038 |
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ISSN: | 2211-1247 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/26095368 |
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Parent Title (English): | Cell reports |
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Publisher: | Cell Press |
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Place of publication: | Maryland Heights, MO |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2015 |
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Date of first Publication: | 2015/06/18 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2016/10/26 |
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Volume: | 11 |
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Issue: | 12 |
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Page Number: | 24 |
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First Page: | 1847 |
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Last Page: | 1855 |
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Note: | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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HeBIS-PPN: | 426718410 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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