Spatio-temporal dynamics of hematopoietic stem cell (HSC) interaction with the HSC niche during migration and engraftment

造血干细胞（HSC）在迁移和植入过程中与 HSC 生态位相互作用的时空动态

• 批准号: 415862770
• 负责人: Dr. Hans Jiro Becker
• 金额: --
• 依托单位: Institute of Medical Science
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/415862770?language=en
• 关键词: Spatio; temporal; dynamics; hematopoietic; stem

Hematopoietic stem cells (HSC) are essential for the continuous supply of healthy blood cells throughout an organism’s life span. For many hematological diseases, stem cell transplantation (SCT) represents the only available curative option. Despite decades of clinical application, the molecular mechanisms that govern successful migration and integration of transplanted HSC from the bloodstream to their target tissues (the stem cell niche) remain widely elusive. Migration of HSCs occurs not only during SCT, but also under steady state conditions. The cells of the HSC niche are thought to be crucial for successful engraftment, yet the lack of appropriate models has so far precluded a comprehensive definition of this HSC-recruiting niche cell population.The aim of this project is to explore the interplay between HSCs and their niche during engraftment. The findings of this study may uncover actionable targets for the modulation of the engraftment process. To this end, we plan to: 1) localize target organs and niches of HSCs and progenitor cells in the early stages (hours to days) of SCT, 2) define niche cells that are crucially involved in HSC engraftment, and 3) identify relevant factors and signals produced by the HSC-recruiting niche cell population. In preparation for this project, the applicant has prepared novel reporter mouse models in the host laboratory that allow for the tracking of HSCs in vivo and permit fluorescence-based visualization of HSC-niche cell interactions. A better understanding of the mechanisms orchestrating HSC engraftment will potentially open new avenues for improving hematologic reconstitution after SCT.

造血干细胞（HSC）是在生物体的整个生命周期中持续供应健康血细胞所必需的。对于许多血液病，干细胞移植（SCT）是唯一可用的治疗选择。尽管有几十年的临床应用，但控制移植的HSC从血流成功迁移和整合到其靶组织（干细胞龛）的分子机制仍然非常难以捉摸。HSC的迁移不仅发生在SCT期间，而且发生在稳态条件下。造血干细胞小生境的细胞被认为是成功植入的关键，但缺乏合适的模型，迄今为止，排除了一个全面的定义，这HSC招募niche细胞population.The项目的目的是探讨造血干细胞和他们的小生境在植入过程中的相互作用。这项研究的结果可能会发现移植过程的调制可操作的目标。为此，我们计划：1）在SCT的早期阶段（数小时至数天）定位HSC和祖细胞的靶器官和小生境，2）定义在HSC植入中至关重要的小生境细胞，3）鉴定HSC募集小生境细胞群产生的相关因子和信号。在该项目的准备中，申请人在宿主实验室中制备了新型报告小鼠模型，该模型允许在体内追踪HSC，并允许基于荧光的HSC-小生境细胞相互作用的可视化。更好地理解HSC植入的机制将为改善SCT后的血液重建开辟新的途径。