Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Cell Stem Cell. 2012 Feb 3;10(2):198-209. doi: 10.1016/j.stem.2012.01.007.
Hematopoietic stem cells (HSCs) are rare multipotent cells that contribute to all blood lineages. During inflammatory stress, hematopoietic stem and progenitor cells (HSPCs) can be stimulated to proliferate and differentiate into the required immune cell lineages. Manipulating signaling pathways that alter HSPC capacity holds great promise in the treatment of hematological malignancies. To date, signaling pathways that influence HSPC capacity, in response to hematopoietic stress, remain largely unknown. Using a zebrafish model of demand-driven granulopoiesis to explore the HSPC response to infection, we present data supporting a model where the zebrafish ortholog of the cytokine-inducible form of nitric oxide synthase (iNOS/NOS2) Nos2a acts downstream of the transcription factor C/ebpβ to control expansion of HSPCs following infection. These results provide new insights into the reactive capacity of HSPCs and how the blood system is "fine-tuned" in response to inflammatory stress.
造血干细胞（HSCs）是一种罕见的多能细胞，可贡献于所有血液谱系。在炎症应激期间，造血干细胞和祖细胞（HSPCs）可被刺激增殖并分化为所需的免疫细胞谱系。操纵改变 HSPC 能力的信号通路在治疗血液恶性肿瘤方面具有巨大的潜力。迄今为止，影响 HSPC 能力的信号通路，以响应造血应激，在很大程度上仍然未知。我们使用了一种需求驱动的粒状细胞发生的斑马鱼模型来探索 HSPC 对感染的反应，提出的数据支持了这样一种模型，即细胞因子诱导型一氧化氮合酶（iNOS/NOS2）的斑马鱼同源物 Nos2a 在转录因子 C/ebpβ 下游发挥作用，以控制感染后 HSPC 的扩增。这些结果为 HSPC 的反应能力以及血液系统如何对炎症应激进行“微调”提供了新的见解。
