Ema Hideo, Sudo Kazuhiro, Seita Jun, Matsubara Azusa, Morita Yohei, Osawa Mitsujiro, Takatsu Kiyoshi, Takaki Satoshi, Nakauchi Hiromitsu
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Dev Cell. 2005 Jun;8(6):907-14. doi: 10.1016/j.devcel.2005.03.019.
Despite being a hallmark of hematopoietic stem cells (HSCs), HSC self-renewal has never been quantitatively assessed. Establishment of a clonal and quantitative assay for HSC function permitted demonstration that adult mouse HSCs are significantly heterogeneous in degree of multilineage repopulation and that higher repopulating potential reflects higher self-renewal activity. An HSC with high repopulating potential could regenerate approximately 1000 HSCs, whereas the repopulating activity of regenerated HSCs on average was significantly reduced, indicating extensive but limited self-renewal capacity in HSCs. Comparisons of wild-type mice with mutant mice deficient in the signal adaptor molecule Lnk showed that not only HSC numbers but also the self-renewal capacity of some HSCs are markedly increased when Lnk function is lost. Lnk appears to control HSC numbers by negatively regulating HSC self-renewal signaling.
尽管自我更新是造血干细胞（HSC）的一个标志，但HSC的自我更新从未得到过定量评估。用于HSC功能的克隆定量分析方法的确立，使得人们能够证明成年小鼠HSC在多谱系重建程度上存在显著异质性，且更高的重建潜力反映出更高的自我更新活性。具有高重建潜力的HSC能够再生大约1000个HSC，而再生HSC的重建活性平均显著降低，这表明HSC具有广泛但有限的自我更新能力。对野生型小鼠与缺乏信号衔接分子Lnk的突变小鼠进行比较发现，当Lnk功能丧失时，不仅HSC数量，而且一些HSC的自我更新能力也会显著增加。Lnk似乎通过负向调节HSC自我更新信号来控制HSC数量。
