Haematopoietic Stem Cell Lab, Cancer Research UK.
Cell Stem Cell. 2013 Aug 1;13(2):161-74. doi: 10.1016/j.stem.2013.05.025.
In addition to well-characterized CD34(+) hematopoietic stem and progenitor cells (HSPCs), the human hematopoietic stem cell (HSC) hierarchy contains a rare CD34(-) population with severe combined immunodeficiency-repopulating capacity. However, little is known about the molecular characteristics of these CD34(-) cells or their relationship to the CD34(+) populations. Here, we show that the self-renewing Lin(-)CD34(-)CD38(-)CD93(hi) population contains cells that not only function as HSCs, but can also be placed above the CD34(+) populations in the hematopoietic hierarchy. These cells have an active Notch pathway, in which signaling through Delta4 is crucial for maintenance of the primitive state, and combined signals from Jagged1 and TGF-β are important in controlling its quiescence. They are also refractory to proliferative signals and show a repressed canonical Wnt pathway, in part regulated by Notch. Overall, therefore, CD34(-) cells represent an immature and quiescent human HSC population maintained through a distinctive network of cellular signaling interactions.
除了特征明确的 CD34(+)造血干细胞和祖细胞 (HSPCs) 外，人类造血干细胞 (HSC) 层次结构还包含具有严重联合免疫缺陷重建能力的罕见 CD34(-)群体。然而，人们对这些 CD34(-)细胞的分子特征或它们与 CD34(+)群体的关系知之甚少。在这里，我们表明，自我更新的 Lin(-)CD34(-)CD38(-)CD93(hi)群体包含不仅作为 HSCs 起作用的细胞，而且还可以在造血层次结构中置于 CD34(+)群体之上。这些细胞具有活跃的 Notch 途径，其中 Delta4 的信号传导对于维持原始状态至关重要，Jagged1 和 TGF-β 的组合信号对于控制其静止状态很重要。它们还对有丝分裂信号具有抗性，并显示出被 Notch 部分调节的受抑制的经典 Wnt 途径。总体而言，因此，CD34(-)细胞代表通过独特的细胞信号相互作用网络维持的不成熟和静止的人类 HSC 群体。
