TY  - JOUR
A1  - Rabenhorst, Uta
A1  - Thalheimer, Frederic Bastian
A1  - Gerlach, Katharina
A1  - Kijonka, Marek
A1  - Böhm, Stefanie
A1  - Krause, Daniela Sandra
A1  - Vauti, Franz
A1  - Arnold, Hans-Henning
A1  - Schroeder, Timm
A1  - Schnütgen, Frank
A1  - Melchner, Harald von
A1  - Rieger, Michael A.
A1  - Zörnig, Martin
T1  - Single-stranded DNA-binding transcriptional regulator FUBP1 is essential for fetal and adult hematopoietic stem cell self-renewal
T2  - Cell reports
N2  - 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.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/41797
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-417977
SN  - 2211-1247
N1  - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 11
IS  - 12
SP  - 1847
EP  - 1855
PB  - Cell Press
CY  - Maryland Heights, MO
ER  -