最新Nature唤醒沉睡的干细胞！

　　

生物通报道，德国海德堡大学德国癌症研究中心细胞生物学系的Andreas Trumpp研究小组在最新的Nature杂志上发表干细胞研究进展，文章标题为：IFNα activates dormant haematopoietic stem cells in vivo。

 

Andreas Trumpp教授是干细胞方面的专家，他主要的研究兴趣在于了解干细胞自我更新与分化机功能的平衡调节机制，干细胞的微环境研究，以及与干细胞相关的致癌或是抑癌的基因机制，开展以上这些研究的最终目的在于为癌症干细胞的诊断还治疗提供理论依据。

 

造血干细胞（hemopoietic stem cell，HSCs）是一种多能干细胞，存在于造血组织中的一群原始造血细胞。在正常骨髓中，多数处于静止期（G0期）。只有在受伤时HSCs才被唤醒，一部分分化成熟，另一部分进行分化增殖。

 

然而，科学家们对唤醒干细胞的机制一无所知。在Andreas的研究过程中，研究小组发现当用当用干扰素阿尔法（IFNα）处理小鼠时，HSCs细胞会迅速地被激活从G0期进入细胞增殖期。IFNα增强STAT1和PKB/Akt的磷酸化作用和IFNα靶位基因的表达作用，上调干细胞抗原1（Sca-1，也称LY6A）的表达量。

 

IFN阿尔法的急性处理有利于促进HSCs的增值作用。这些研究成果可能解释IFNα对于白血病的临床作用效果，同时也为处理白血病癌症干细胞提供了新的方法。

（生物通 小茜）

  

了解Eppendorf的癌症研究芯片资讯

 

生物通推荐原文检索：IFNα activates dormant haematopoietic stem cells in vivo

【Abstract】

Maintenance of the blood system is dependent on dormant haematopoietic stem cells (HSCs) with long-term self-renewal capacity. After injury these cells are induced to proliferate to quickly re-establish homeostasis1. The signalling molecules promoting the exit of HSCs out of the dormant stage remain largely unknown. Here we show that in response to treatment of mice with interferon- (IFN), HSCs efficiently exit G0 and enter an active cell cycle. HSCs respond to IFN treatment by the increased phosphorylation of STAT1 and PKB/Akt (also known as AKT1), the expression of IFN target genes, and the upregulation of stem cell antigen-1 (Sca-1, also known as LY6A). HSCs lacking the IFN/ receptor (IFNAR)2, STAT1 (ref. 3) or Sca-1 (ref. 4) are insensitive to IFN stimulation, demonstrating that STAT1 and Sca-1 mediate IFN-induced HSC proliferation. Although dormant HSCs are resistant to the anti-proliferative chemotherapeutic agent 5-fluoro-uracil1, 5, HSCs pre-treated (primed) with IFN and thus induced to proliferate are efficiently eliminated by 5-fluoro-uracil exposure in vivo. Conversely, HSCs chronically activated by IFN are functionally compromised and are rapidly out-competed by non-activatable Ifnar-/- cells in competitive repopulation assays. Whereas chronic activation of the IFN pathway in HSCs impairs their function, acute IFN treatment promotes the proliferation of dormant HSCs in vivo. These data may help to clarify the so far unexplained clinical effects of IFN on leukaemic cells, and raise the possibility for new applications of type I interferons to target cancer stem cells.