造血干细胞（HSCs）以休眠状态存在，直到在受伤时才被唤醒，从而发生增殖，以快速修复损伤的组织。这篇论文表明，当用干扰素阿尔法（IFNα）处理小鼠时，为响应这种处理，HSCs进入一个活动细胞周期，增加STAT1 和 PKB/Akt的磷酸化，抑制IFNα目标基因，同时向上调节干细胞抗原-1（Sca-1）。虽然HSCs中IFNα通道的慢性激发会损害这一功能，但急性IFNα处理却能在活体中促进休眠HSCs的增殖。
这些数据也许可帮助澄清迄今尚未得到解释的IFNα对于白血病细胞的临床效应，同时也提出了利用I-型干扰素来定向处理癌症干细胞的新应用的可能性。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 458, 904-908 (16 April 2009) | doi:10.1038/nature07815
IFNα activates dormant haematopoietic stem cells in vivo
Marieke A. G. Essers1,2, Sandra Offner3, William E. Blanco-Bose3, Zoe Waibler4, Ulrich Kalinke4,5, Michel A. Duchosal6 & Andreas Trumpp1,2,3
1 Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
2 Heidelberg Institute for Stem Cell Technologies and Experimental Medicine (HI-STEM), Im Neuenheimer Feld 280. D-69120 Heidelberg, Germany
3 Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC—Swiss Institute for Experimental Cancer Research, School of Life Science, 1015 Lausanne, Switzerland
4 Division of Immunology, Paul Ehrlich Institute, D-63225 Langen, Germany
5 TWINCORE—Centre for Experimental and Clinical Infection Research Feodor-Lynen-Str. 7, 30625 Hannover, Germany
6 Service and Central Laboratory of Hematology, CHUV, University Hospitals of Lausanne, CH-1011 Lausanne, Switzerland
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-α (IFNα), HSCs efficiently exit G0 and enter an active cell cycle. HSCs respond to IFNα 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 IFNα stimulation, demonstrating that STAT1 and Sca-1 mediate IFN-induced HSC proliferation. Although dormant HSCs are resistant to the anti-αproliferative 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 IFNα pathway in HSCs impairs their function, acute IFNα 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 cells6, 7, and raise the possibility for new applications of type I interferons to target cancer stem cells8.
