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| Content Provider | PubMed Central |
|---|---|
| Author | Wang, Yong Schulte, Bradley A. Larue, Amanda C. Ogawa, Makio Zhou, Daohong |
| Copyright Year | 2006 |
| 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, p16Ink4a and SA-β-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 p21Cip1/Waf1, p19Arf, and p16Ink4a mRNA expression, while the expression of p27Kip1 and p18Ink4c mRNA was not increased following TBI. This suggests that p21Cip1/Waf1, p19Arf, and p16Ink4a may play an important role in IR-induced senescence in HSCs. |
| Related Links | http://dx.doi.org/10.1182/blood-2005-04-1418 |
| Starting Page | 358 |
| File Format | |
| ISSN | 15280020 |
| e-ISSN | 15280020 |
| Journal | Blood |
| Issue Number | 1 |
| Volume Number | 107 |
| Language | English |
| Publisher | © 2006 by The American Society of Hematology |
| Publisher Date | 2006-01-01 |
| Access Restriction | Open |
| Rights Holder | © 2006 by The American Society of Hematology |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Hematology Biochemistry Immunology |
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