Total Body Irradiation Selectively Induces Murine Hematopoietic Stem Cell Senescence.
From: Department of Pathology & Laboratory Medicine, MUSC, 165 Ashley Ave, Suite 309, Charleston, SC 29425, USA.
Blood
- Publish Date: Jan 2006
- ISSN: 0006-4971
- Volume: 107
- Issue: 1
- Pages: 358-66
- Medium: Print
- Language: English
- Citation (JAMA): Wang Yong, Schulte Bradley A, LaRue Amanda C, et al. Total Body Irradiation Selectively Induces Murine Hematopoietic Stem Cell Senescence.. Blood Jan 2006;107:358-66
Abstract
Exposure to ionizing radiation (IR) and certain chemotherapeutic agents not only causes acute bone marrow (BM) suppression but also leads to long-term residual hematopoietic injury. This latter effect has been attributed to damage to hematopoietic stem cell (HSC) self-renewal. Using a mouse model, we investigated whether IR induces senescence in HSCs, as induction of HSC senescence can lead to the defect in HSC self-renewal. It was found that exposure of C57BL/6 mice to a sublethal dose (6.5 Gy) of total body irradiation (TBI) resulted in a sustained quantitative and qualitative reduction of LKS+ HSCs. In addition, LKS+ HSCs from irradiated mice exhibited an increased expression of the 2 commonly used biomarkers of cellular senescence, p16(Ink4a) and SA-beta-gal. In contrast, no such changes were observed in irradiated LKS- hematopoietic progenitor cells. These results provide the first direct evidence demonstrating that IR exposure can selectively induce HSC senescence. Of interest, the induction of HSC senescence was associated with a prolonged elevation of p21(Cip1/Waf1), p19(Arf), and p16(Ink4a) mRNA expression, while the expression of p27(Kip1) and p18(Ink4c) mRNA was not increased following TBI. This suggests that p21(Cip1/Waf1), p19(Arf), and p16(Ink4a) may play an important role in IR-induced senescence in HSCs.
Mesh Headings (Keywords): Animals, Cell Aging, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p19, Cyclin-Dependent Kinase Inhibitor p21, Hematopoietic Stem Cells, Male, Mice, Mice, Inbred C57BL, RNA, Messenger, Up-Regulation, Whole-Body Irradiation
Check for Full Text / PubMed Unique Identifier (PMID): 16150936
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