Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schraml, E; Voglauer, R; Fortschegger, K; Sibilia, M; Stelzer, I; Grillari, J; Schauenstein, K.
Haploinsufficiency of senescence evasion factor causes defects of hematopoietic stem cells functions.
STEM CELLS DEV. 2008; 17(2): 355-366.
Doi: 10.1089/scd.2007.0107
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Schraml Elisabeth
- Co-Autor*innen der Med Uni Graz
- Schauenstein Konrad
- Stelzer Ingeborg
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- The quality of hematopoietic stem cells (HSCs) is essentially defined by two characteristics, i.e., multilineage differentiation and self-renewal capacity. Thus, it is of high priority to clarify mechanisms that regulate these functions and to understand them at the molecular level. In the present study, we investigated the role of senescence evasion factor (synonymously hPrp19,hPSO4,hNMP200: SNEV), a multifunctional protein involved in pre-mRNA splicing, regulation of replicative life span, and DNA repair. Here we report that murine SNEV mRNA expression is high in lineage-depleted (Lin(-)) precursor cells of the bone marrow immediately after isolation as compared to fully differentiated peripheral blood lymphocytes (PBLs). Furthermore, the progenitor cell subset with highest colony-forming ability and self-renewal capacity (Lin(-), Sca-1(+)) showed also the highest SNEV expression. To test if the observed differences in SNEV mRNA levels cause stem cell defects, Lin(-) cells derived from heterozygous SNEV knockout mice were tested for primary as well as secondary colony-forming potential as a measure of self-renewal capacity. Interestingly, both, primary and secondary colonies were significantly less formed from SNEV(+/-) cells, a defect that was rescued by ectopic SNEV expression. Similarly, bone marrow cells derived from the short-lived Senescence-Accelerated-Mouse-Prone (SAMP8) model showed similar differences in comparison to the aging-resistant (SAMR1) control strain. These data suggest that the expression of SNEV is closely associated with the growth of murine HSCs and determines the proliferative and repopulating capacity of phenotypically defined HSC subsets.
- Find related publications in this database (using NLM MeSH Indexing)
- Allelic Imbalance - physiology
- Animals -
- Blood Cells - metabolism
- Bone Marrow Cells - metabolism
- Cell Differentiation - genetics
- Cell Proliferation -
- Cells, Cultured -
- Female -
- Hematopoietic Stem Cells - metabolism
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Nuclear Matrix-Associated Proteins - genetics