Department of Bioengineering, Rice University, Houston, TX 77005.
Center for Human Immunobiology, Texas Children's Hospital, Houston, TX 77030.
Mol Biol Cell. 2017 Dec 1;28(25):3573-3581. doi: 10.1091/mbc.E17-08-0508. Epub 2017 Oct 11.
Human natural killer (NK) cells are generated from CD34 precursors and can be differentiated in vitro by coculture with developmentally supportive stromal cells. We have previously described the acquisition of cell migration as a feature of NK cell terminal maturation in this system. Here we perform continuous long-term imaging and tracking of NK cell progenitors undergoing in vitro differentiation. We demonstrate that NK cell precursors can be tracked over long time periods on the order of weeks by utilizing phase-contrast microscopy and show that these cells acquire increasing motility as they mature. Additionally, we observe that NK cells display a more heterogeneous range of migratory behaviors at later stages of development, with the acquisition of complex modes of migration that are associated with terminal maturation. Together these data demonstrate previously unknown migratory behaviors of innate lymphocytes undergoing lineage differentiation revealed by long-term imaging and analysis workflows.
人类自然杀伤 (NK) 细胞由 CD34 前体细胞产生，并可通过与发育支持基质细胞共培养在体外分化。我们之前描述了在该系统中作为 NK 细胞终末成熟特征的细胞迁移的获得。在这里，我们对体外分化过程中的 NK 细胞前体进行连续的长期成像和跟踪。我们通过利用相差显微镜证明，NK 细胞前体可以在数周的时间内进行长时间的跟踪，并显示出这些细胞在成熟过程中获得了越来越强的迁移能力。此外，我们还观察到 NK 细胞在发育的后期表现出更异质的迁移行为范围，获得了与终末成熟相关的复杂迁移模式。这些数据共同证明了通过长期成像和分析工作流程揭示的固有淋巴细胞在谱系分化过程中以前未知的迁移行为。
