Department of Bioengineering, Rice University, Houston, TX 77005.
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Mol Biol Cell. 2020 May 1;31(10):981-991. doi: 10.1091/mbc.E19-08-0424.
Lymphocyte development is a complex and coordinated pathway originating from pluripotent stem cells during embryogenesis and continuing even as matured lymphocytes are primed and educated in adult tissue. Hematopoietic stem cells develop in a specialized niche that includes extracellular matrix and supporting stromal and endothelial cells that both maintain stem cell pluripotency and enable the generation of differentiated cells. Cues for lymphocyte development include changes in integrin-dependent cell motility and adhesion which ultimately help to determine cell fate. The capacity of lymphocytes to adhere and migrate is important for modulating these developmental signals both by regulating the cues that the cell receives from the local microenvironment as well as facilitating the localization of precursors to tissue niches throughout the body. Here we consider how changing migratory and adhesive phenotypes contribute to human natural killer (NK)- and T-cell development as they undergo development from precursors to mature, circulating cells and how our understanding of this process is informed by in vitro models of T- and NK cell generation.
淋巴细胞的发育是一个复杂而协调的过程，始于胚胎发生过程中的多能干细胞，并在成熟的淋巴细胞在成人组织中被启动和教育时继续进行。造血干细胞在一个特殊的龛位中发育，其中包括细胞外基质和支持的基质和成内皮细胞，它们既能维持干细胞的多能性，又能产生分化细胞。淋巴细胞发育的线索包括整合素依赖性细胞迁移和黏附的变化，这最终有助于确定细胞命运。淋巴细胞的黏附和迁移能力对于调节这些发育信号很重要，因为它既可以调节细胞从局部微环境中接收到的线索，也可以促进前体细胞向全身组织龛位的定位。在这里，我们考虑了在从前体细胞到成熟的循环细胞的发育过程中，改变迁移和黏附表型如何促进人类自然杀伤（NK）和 T 细胞的发育，以及我们对这一过程的理解如何通过体外 T 和 NK 细胞生成模型得到证实。
