Single-stranded DNA-binding transcriptional regulator FUBP1 is essential for fetal and adult hematopoietic stem cell self-renewal

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 transcrip
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.
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Author: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
URN:urn:nbn:de:hebis:30:3-417977
DOI:http://dx.doi.org/10.1016/j.celrep.2015.05.038
ISSN:2211-1247
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26095368
Parent Title (English):Cell reports
Publisher:Cell Press
Place of publication:Maryland Heights, MO
Document Type:Article
Language:English
Year of Completion:2015
Date of first Publication:2015/06/18
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2016/10/26
Volume:11
Issue:12
Pagenumber:24
First Page:1847
Last Page:1855
Note:
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
HeBIS PPN:426718410
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0

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