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Blood, 1 January 2006, Vol. 107, No. 1, pp. 358-366. Prepublished online as a Blood First Edition Paper on September 8, 2005; DOI 10.1182/blood-2005-04-1418. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1418v1 107/1/358    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Zhou, D. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Zhou, D. Related Collections Cell Cycle Gene Expression Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY Total body irradiation selectively induces murine hematopoietic stem cell senescence Yong Wang, Bradley A. Schulte, Amanda C. LaRue, Makio Ogawa, and Daohong Zhou From the Departments of Pathology and Laboratory Medicine and the Department of Medicine, Medical University of South Carolina, Charleston, SC; and the Department of Veterans Affairs Medical Center, Charleston, SC. 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--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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Marusyk, M. Casas-Selves, C. J. Henry, V. Zaberezhnyy, J. Klawitter, U. Christians, and J. DeGregori Irradiation Alters Selection for Oncogenic Mutations in Hematopoietic Progenitors Cancer Res., September 15, 2009; 69(18): 7262 - 7269. [Abstract] [Full Text] [PDF] K. Nakade, J. Pan, T. Yamasaki, T. Murata, B. Wasylyk, and K. K. Yokoyama JDP2 (Jun Dimerization Protein 2)-deficient Mouse Embryonic Fibroblasts Are Resistant to Replicative Senescence J. Biol. Chem., April 17, 2009; 284(16): 10808 - 10817. [Abstract] [Full Text] [PDF] M. W. Bergmann, L. Zelarayan, and C. Gehrke Treatment-Sensitive Premature Renal and Heart Senescence in Hypertension Hypertension, July 1, 2008; 52(1): 61 - 62. [Full Text] [PDF] K. Venkataraman, Y.-M. Lee, J. Michaud, S. Thangada, Y. Ai, H. L. Bonkovsky, N. S. Parikh, C. Habrukowich, and T. Hla Vascular Endothelium As a Contributor of Plasma Sphingosine 1-Phosphate Circ. Res., March 28, 2008; 102(6): 669 - 676. [Abstract] [Full Text] [PDF] F. Rodier, J. Campisi, and D. Bhaumik Two faces of p53: aging and tumor suppression Nucleic Acids Res., December 3, 2007; 35(22): 7475 - 7484. [Abstract] [Full Text] [PDF] S. J. Neering, T. Bushnell, S. Sozer, J. Ashton, R. M. Rossi, P.-Y. Wang, D. R. Bell, D. Heinrich, A. Bottaro, and C. T. Jordan Leukemia stem cells in a genetically defined murine model of blast-crisis CML Blood, October 1, 2007; 110(7): 2578 - 2585. [Abstract] [Full Text] [PDF] J. Ma, M. Shi, J. Li, B. Chen, H. Wang, B. Li, J. Hu, Y. Cao, B. Fang, and R. C. Zhao Senescence-unrelated impediment of osteogenesis from Flk1+ bone marrow mesenchymal stem cells induced by total body irradiation and its contribution to long-term bone and hematopoietic injury Haematologica, July 1, 2007; 92(7): 889 - 896. [Abstract] [Full Text] [PDF] C. T. Jordan, M. L. Guzman, and M. Noble Cancer stem cells. N. Engl. J. Med., September 21, 2006; 355(12): 1253 - 1261. [Full Text] [PDF] H. Yu, Y. Yuan, H. Shen, and T. Cheng Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners Blood, February 1, 2006; 107(3): 1200 - 1206. [Abstract] [Full Text] [PDF]

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