Journal
STEM CELL RESEARCH
Volume 11, Issue 2, Pages 687-692Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2013.04.010
Keywords
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Funding
- NIH [2 P01 HL048546-16A1]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL048546] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM071338] Funding Source: NIH RePORTER
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Fanconi anemia patients suffer from progressive bone marrow failure. An overactive p53 response to DNA damage contributes to the progressive elimination of Fanconi anemia hematopoietic stem and progenitor cells (HSPC), and hence presents a potential target for therapeutic intervention. To investigate whether the cell cycle regulatory protein p21 is the primary mediator of the p53-dependent stem cell toss, p21/Fancd2 double-knockout mice were generated. Surprisingly double mutant mice displayed even more severe loss of HSPCs than Fancd2(-/-) single mutants. p21 deletion did not rescue the abnormal cell cycle profile and had no impact on the long-term repopulating potential of Fancd2(-/-) bone marrow cells. Collectively, our data indicate that p21 has an indispensable role in maintaining a normal HSPC pool and suggest that other p53-targeted factors, not p21, mediate the progressive elimination of HSPC in Fanconi anemia. (C) 2013 Elsevier B.V. All rights reserved.
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