Hedgehog signaling is dispensable for adult hematopoietic stem cell function.
Hedgehog signaling is dispensable for adult hematopoietic stem cell function.
复制标题
DOI：
10.1016/j.stem.2009.03.015
复制
发表时间：
2009-06-05
期刊：
影响因子：
23.9
通讯作者：
Aifantis I
中科院分区：
文献类型：
--
作者：
Gao J;Graves S;Koch U;Liu S;Jankovic V;Buonamici S;El Andaloussi A;Nimer SD;Kee BL;Taichman R;Radtke F;Aifantis I
Hedgehog（Hh）信号通路是干细胞功能的发育保守调节因子。一些研究表明，Hh信号是造血干细胞（HSC）维持和分化的重要调节因子。在这里，我们测试这一假设在体内使用的增益和损失的功能Hh遗传模型。令人惊讶的是，我们的研究表明，条件性Smoothened（Smo）缺失或过度激活对成体HSC的自我更新和功能没有显着影响。此外，它们表明在HSC功能中Notch和Hh途径之间缺乏协同作用，因为化合物RBPJ-和Smo-缺乏不影响造血。与这一观点一致，详细的全基因组转录组分析揭示，Hh信号转导的沉默不会显著改变HSC特异性基因表达“签名”。我们的研究表明，Hh信号通路是成年HSC功能的抑制剂，并表明Hh通路可以在未来的临床试验中靶向Hh抑制对白血病起始细胞维持的影响。
The Hedgehog (Hh) signaling pathway is a developmentally conserved regulator of stem cell function. Several reports suggested that Hh signaling is an important regulator of hematopoietic stem cell (HSC) maintenance and differentiation. Here we test this hypothesis in vivo using both gain- and loss-of-function Hh genetic models. Surprisingly, our studies demonstrate that conditional Smoothened (Smo) deletion or over-activation has no significant effects on adult HSC self-renewal and function. Moreover, they indicate a lack of synergism between the Notch and Hh pathways in HSC function, as compound RBPJ- and Smo-deficiency does not affect hematopoiesis. In agreement with this notion, detailed genome-wide transcriptome analysis reveals that silencing of Hh signaling does not significantly alter the HSC-specific gene expression “signature”. Our studies demonstrate that the Hh signaling pathway is dispensable for adult HSC function and suggest that the Hh pathway can be targeted in future clinical trials addressing the effect of Hh inhibition on leukemia-initiating cell maintenance.
登录
查看更多内容
影响因子：
82.9
作者：
Dierks, Christine;Grbic, Jovana;Warmuth, Markus
通讯作者：
Warmuth, Markus
影响因子：
32.4
作者：
Mansson, Robert;Hultquist, Anne;Jacobsen, Sten Eirik W.
通讯作者：
Jacobsen, Sten Eirik W.
影响因子：
4.4
作者：
Han, H;Tanigaki, K;Honjo, T
通讯作者：
Honjo, T
影响因子：
30.5
作者：
El Abdaloussi, E;Graves, S;Aifantis, I
通讯作者：
Aifantis, I
影响因子：
30.5
作者：
Bhardwaj, G;Murdoch, B;Bhatia, M
通讯作者：
Bhatia, M