Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
复制标题
DOI：
10.1016/j.stem.2008.09.005
复制
发表时间：
2008-12-04
期刊：
影响因子：
23.9
通讯作者：
Trumpp A
中科院分区：
文献类型：
--
作者：
Laurenti E;Varnum-Finney B;Wilson A;Ferrero I;Blanco-Bose WE;Ehninger A;Knoepfler PS;Cheng PF;MacDonald HR;Eisenman RN;Bernstein ID;Trumpp A
Myc活性正在成为获得和维持干细胞特性的关键因素。我们先前已经表明，c-Myc缺陷导致由于小生境依赖性分化缺陷而导致的有缺陷的造血干细胞（HSC）的积累。在这里，我们报告，未成熟的HSC共表达c-myc和N-myc mRNA在相似的水平。尽管骨髓中N-myc的条件性缺失不影响造血，但c-Myc和N-Myc的联合缺乏（dKO）导致全血细胞减少和快速致死。有趣的是，HSC的增殖在稳态期间依赖于两个myc基因，但在损伤后的骨髓修复期间是c-Myc/N-Myc独立的。引人注目的是，虽然大多数dKO造血细胞经历细胞凋亡，但只有自我更新的HSC积累通常由先天免疫系统使用的细胞毒性分子GranzymeB，从而揭示了干细胞凋亡的意想不到的机制。总的来说，Myc活性（c-Myc和N-Myc）控制HSC功能的关键方面，包括增殖、分化和存活。
Myc activity is emerging as a key element in acquisition and maintenance of stem cell properties. We have previously shown that c-Myc deficiency results in accumulation of defective hematopoietic stem cells (HSCs) due to niche-dependent differentiation defects. Here we report that immature HSCs coexpress c-myc and N-myc mRNA at similar levels. Although conditional deletion of N-myc in the bone marrow does not affect hematopoiesis, combined deficiency of c-Myc and N-Myc (dKO) results in pancytopenia and rapid lethality. Interestingly, proliferation of HSCs depends on both myc genes during homeostasis, but is c-Myc/N-Myc independent during bone marrow repair after injury. Strikingly, while most dKO hematopoietic cells undergo apoptosis, only self-renewing HSCs accumulate the cytotoxic molecule GranzymeB, normally employed by the innate immune system, thereby revealing an unexpected mechanism of stem cell apoptosis. Collectively, Myc activity (c-Myc and N-Myc) controls crucial aspects of HSC function including proliferation, differentiation, and survival.
登录
查看更多内容
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
8
作者：
Cole, MD;McMahon, SB
通讯作者：
McMahon, SB
影响因子：
4.6
作者：
Cartwright, P;McLean, C;Dalton, S
通讯作者：
Dalton, S
影响因子：
4.6
作者：
Dubois, Nicole C.;Adolphe, Christelle;Trumpp, Andreas
通讯作者：
Trumpp, Andreas
影响因子：
11.4
作者：
Knoepfler, Paul S.;Zhang, Xiao-yong;Eisenman, Robert N.
通讯作者：
Eisenman, Robert N.