Intrinsic and environmental influences on thymocyte migration signatures

对胸腺细胞迁移特征的内在和环境影响

• 批准号: RGPIN-2019-05053
• 负责人: Melichar, Heather
• 金额: $ 2.99万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714553
• 关键词: Intrinsic; environmental; influences; thymocyte; migration

Cell migration is important for a number of biological processes including cell and tissue development. The behavior of migrating cells is incredibly diverse: some cells migrate slowly and others fast, some cells travel along a fairly straight path to a specific destination while others migrate tortuously with no obvious directionality, and some migrate individually whereas others move as a group. Why certain migration patterns are associated with particular cell types and what factors influence these migration signatures is not well described for many cell subsets. As a model to address these biological questions, we study the migration patterns of a subtype of immune cells called T cells as they develop in the thymus. The progenitor cells that seed the thymus transit through a series of well-characterized developmental intermediates, and thymocytes (immature T cells) at each stage of development display distinct migration signatures. During one developmental transition in particular, thymocytes more than double their speed transitioning from slow, meandering cells into cells that move with increased straightness and become among the fastest cells in the body. These developmental stages occur in distinct locations in the thymus, but the factors that influence their migratory signatures are not well described. We use a unique organ culture system and advanced microscopy techniques to visualize the dynamic migration of developing T cells in intact thymus tissue in order to identify the factors that influence migration patterns and determine how modulating these movements influence T cell development. In addition, we apply image analyses and machine learning approaches to identify cell subsets within a heterogeneous population based on their migration signature in intact tissue. Ultimately, these studies will contribute to our understanding of how cell migration is optimized for proper development and function of developing T cells, other immune cells, and beyond. Further, in the context of this research program several undergraduate and graduate students will receive interdisciplinary training using state-of-the-art technologies that will equip them with the skills they need to excel in the burgeoning fields of immunology and biophotonics in Canada.

细胞迁移对于包括细胞和组织发育在内的许多生物过程很重要。迁移细胞的行为极其多样化：有些细胞迁移缓慢，有些细胞迁移快速；有些细胞沿着相当笔直的路径到达特定目的地，而另一些细胞则曲折地迁移，没有明显的方向性；有些细胞单独迁移，而另一些细胞则作为群体移动。对于许多细胞亚群来说，为什么某些迁移模式与特定细胞类型相关以及哪些因素影响这些迁移特征尚未得到很好的描述。作为解决这些生物学问题的模型，我们研究了一种称为 T 细胞的免疫细胞亚型在胸腺中发育时的迁移模式。接种胸腺的祖细胞会经历一系列特征明确的发育中间体，而胸腺细胞（未成熟​​的 T 细胞）在每个发育阶段都表现出不同的迁移特征。特别是在一个发育转变过程中，胸腺细胞的速度增加了一倍以上，从缓慢、蜿蜒的细胞转变为直线运动的细胞，并成为体内最快的细胞之一。这些发育阶段发生在胸腺的不同位置，但影响其迁移特征的因素尚未得到很好的描述。我们使用独特的器官培养系统和先进的显微镜技术来可视化完整胸腺组织中发育中 T 细胞的动态迁移，以确定影响迁移模式的因素并确定调节这些运动如何影响 T 细胞发育。此外，我们应用图像分析和机器学习方法，根据完整组织中的迁移特征来识别异质群体中的细胞子集。最终，这些研究将有助于我们了解如何优化细胞迁移，以实现发育中 T 细胞、其他免疫细胞等的正常发育和功能。此外，在该研究计划的背景下，一些本科生和研究生将接受使用最先进技术的跨学科培训，这将使他们具备在加拿大新兴的免疫学和生物光子学领域脱颖而出所需的技能。