TY - JOUR
T1 - Fancd2 and p21 function independently in maintaining the size of hematopoietic stem and progenitor cell pool in mice
AU - Zhang, Qing Shuo
AU - Watanabe-Smith, Kevin
AU - Schubert, Kathryn
AU - Major, Angela
AU - Sheehan, Andrea M.
AU - Marquez-Loza, Laura
AU - Newell, Amy E.Hanlon
AU - Benedetti, Eric
AU - Joseph, Eric
AU - Olson, Susan
AU - Grompe, Markus
N1 - Funding Information:
This work was supported by NIH grant 2 P01 HL048546-16A1 .
PY - 2013/9
Y1 - 2013/9
N2 - 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 loss, 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.
AB - 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 loss, 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.
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U2 - 10.1016/j.scr.2013.04.010
DO - 10.1016/j.scr.2013.04.010
M3 - Article
C2 - 23721813
AN - SCOPUS:84878408247
SN - 1873-5061
VL - 11
SP - 687
EP - 692
JO - Stem Cell Research
JF - Stem Cell Research
IS - 2
ER -