Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Cell. 2011 Dec 23;147(7):1589-600. doi: 10.1016/j.cell.2011.11.041.
Maintenance of a hematopoietic progenitor population requires extensive interaction with cells within a microenvironment or niche. In the Drosophila hematopoietic organ, niche-derived Hedgehog signaling maintains the progenitor population. Here, we show that the hematopoietic progenitors also require a signal mediated by Adenosine deaminase growth factor A (Adgf-A) arising from differentiating cells that regulates extracellular levels of adenosine. The adenosine signal opposes the effects of Hedgehog signaling within the hematopoietic progenitor cells and the magnitude of the adenosine signal is kept in check by the level of Adgf-A secreted from differentiating cells. Our findings reveal signals arising from differentiating cells that are required for maintaining progenitor cell quiescence and that function with the niche-derived signal in maintaining the progenitor state. Similar homeostatic mechanisms are likely to be utilized in other systems that maintain relatively large numbers of progenitors that are not all in direct contact with the cells of the niche.
造血祖细胞群体的维持需要与微环境或龛内的细胞进行广泛的相互作用。在果蝇造血器官中，龛衍生的 Hedgehog 信号维持祖细胞群体。在这里，我们表明造血祖细胞还需要一种由分化细胞产生的信号介导，这种信号由腺苷脱氨酶生长因子 A (Adgf-A) 介导，调节细胞外腺苷水平。腺苷信号在造血祖细胞内对抗 Hedgehog 信号的作用，并且由分化细胞分泌的 Adgf-A 水平来控制腺苷信号的幅度。我们的发现揭示了来自分化细胞的信号，这些信号对于维持祖细胞静止是必需的，并且与龛衍生的信号一起发挥作用，以维持祖细胞状态。在维持数量相对较多的祖细胞的其他系统中，可能利用了类似的动态平衡机制，而这些祖细胞并非都与龛细胞直接接触。
