The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.
The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells.
复制标题
泛素连接酶 Huwe1 调节造血干细胞的维持和淋巴定向。
作者：
造血干细胞（HSCs）在骨髓中处于休眠状态，可以在各种压力下被激活，以补充所有类型的血细胞。在这里，我们确定泛素连接酶Huwe 1作为一个重要的调节HSC功能，通过其翻译后控制N-myc。我们发现Huwe 1是HSC自我更新，静止和淋巴命运规范所必需的。使用一种新的荧光融合等位基因（MycnM），我们观察到，N-myc的表达仅限于最不成熟的，多能干细胞和祖细胞群体。N-myc在应激或Huwe 1缺失时上调，导致增殖增加和干细胞耗竭。Mycn耗竭逆转了体内大多数这些表型，表明Huwe 1对N-myc的衰减对于在应激后重建稳态至关重要。
Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. Here we identify the ubiquitin ligase Huwe1 as a crucial regulator of HSC functions via its post-translational control of N-myc. We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid fate specification. Using a novel fluorescent fusion allele (MycnM), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations. N-myc was upregulated in response to stress or upon loss of Huwe1, leading to increased proliferation and stem cell exhaustion. Mycn depletion reversed most of these phenotypes in vivo, suggesting that the attenuation of N-myc by Huwe1 is essential to reestablish homeostasis following stress.
登录
查看更多内容
影响因子：
23.9
作者：
Liu Y;Elf SE;Miyata Y;Sashida G;Liu Y;Huang G;Di Giandomenico S;Lee JM;Deblasio A;Menendez S;Antipin J;Reva B;Koff A;Nimer SD
通讯作者：
Nimer SD
影响因子：
8.7
作者：
Kondo M
通讯作者：
Kondo M
影响因子：
4.5
作者：
Phelan, James D.;Saba, Ingrid;Grimes, H. Leighton
通讯作者：
Grimes, H. Leighton
DOI：
10.1126/science.1256271
发表时间：
2014-08-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lara-Astiaso D;Weiner A;Lorenzo-Vivas E;Zaretsky I;Jaitin DA;David E;Keren-Shaul H;Mildner A;Winter D;Jung S;Friedman N;Amit I
通讯作者：
Amit I
影响因子：
5.3
作者：
BARRETT, J;BIRRER, MJ;DANG, CV
通讯作者：
DANG, CV