Fancd2 and p21 function independently in maintaining the size of hematopoietic stem and progenitor cell pool in mice.
Fancd2 and p21 function independently in maintaining the size of hematopoietic stem and progenitor cell pool in mice.
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FANCD2和P21独立于保持小鼠造血茎和祖细胞库的大小。
DOI：
10.1016/j.scr.2013.04.010
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发表时间：
2013-09
影响因子：
1.2
通讯作者：
Grompe, Markus
中科院分区：
文献类型：
--
作者：
Zhang, Qing-Shuo;Watanabe-Smith, Kevin;Schubert, Kathryn;Major, Angela;Sheehan, Andrea M.;Marquez-Loza, Laura;Newell, Amy E. Hanlon;Benedetti, Eric;Joseph, Eric;Olson, Susan;Grompe, Markus
范可尼贫血患者患有进行性骨髓衰竭。过度活跃的p53对DNA损伤的反应有助于逐步消除范可尼贫血的造血干细胞和祖细胞（HSPC），因此提供了治疗干预的潜在靶点。为了研究细胞周期调节蛋白p21是否是p53依赖性干细胞丢失的主要介质，我们制造了p21/Fancd2双敲除小鼠。令人惊讶的是，双突变小鼠比Fancd2−/−单突变小鼠表现出更严重的HSPCs丢失。p21缺失不能挽救异常的细胞周期谱，也对Fancd2−/−骨髓细胞的长期再生潜力没有影响。总的来说，我们的数据表明p21在维持正常的HSPC池中起着不可或缺的作用，并表明其他p53靶向因子介导了Fanconi贫血中HSPC的逐渐消除，而不是p21。
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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影响因子：
20.3
作者：
Kutler, DI;Singh, B;Auerbach, AD
通讯作者：
Auerbach, AD
影响因子：
11.2
作者：
Zhang, Qing-Shuo;Eaton, Laura;Grompe, Markus
通讯作者：
Grompe, Markus
影响因子：
20.3
作者：
Freie, B;Li, XX;Clapp, DW
通讯作者：
Clapp, DW
影响因子：
23.9
作者：
Ceccaldi, Raphael;Parmar, Kalindi;Mouly, Enguerran;Delord, Marc;Kim, Jung Min;Regairaz, Marie;Pla, Marika;Vasquez, Nadia;Zhang, Qing-Shuo;Pondarre, Corinne;de Latour, Regis Peffault;Gluckman, Eliane;Cavazzana-Calvo, Marina;Leblanc, Thierry;Larghero, Jerome;Grompe, Markus;Socie, Gerard;D'Andrea, Alan D.;Soulier, Jean
通讯作者：
Soulier, Jean
影响因子：
56.9
作者：
Cheng, T;Rodrigues, N;Scadden, DT
通讯作者：
Scadden, DT