The Impact of Cell and Gene Therapy on the Function and Molecular Regulation of Hematopoietic Stem Cells.

造血是一个复杂的细胞过程，允许在生物体的一生中产生和进一步维持多种功能性血细胞。造血干细胞（hsc）是造血系统的基础，具有自我更新和产生谱系特异性祖细胞的潜力。造血干细胞扩展和分化的基本特性引起了人们对其在一系列造血疾病的基因治疗中的应用的兴趣。然而，基因治疗对造血干细胞潜在生物学的分子影响仍然知之甚少。该项目旨在通过结合单细胞转录组学、慢病毒转导技术、流式细胞术和单细胞功能分析来解决该领域尚未解决的问题。重要的是，所进行的研究将提高我们对造血干细胞如何应对压力的整体理解，并有助于确定基因治疗是否是一种安全有效的治疗手段。从这个项目中获得的结果也有可能指导未来基因治疗方案的改进，以增加转导后造血干细胞的功能。

Haematopoiesis is an intricate cellular process allowing the generation and further maintenance of a diverse repertoire of functional blood cellsthroughout an organisms' lifetime. Hematopoietic stem cells (HSCs) constitute the foundation of the hematopoietic hierarchy and have the potential toboth self-renew and produce lineage specific progenitors. The fundamental properties of HSCs to expand and differentiate have provoked interest intheir application in gene therapy for the treatment of a range of hematopoietic diseases. However, the molecular consequences of gene therapy on theunderlying biology of HSCs remains poorly understood. This project aims to address unanswered areas in the field by combining single celltranscriptomics, lentiviral transduction technology, flow cytometry and single cell functional assays. Importantly, research conducted will both improveour overall understanding of how HSCs respond to stress and help to determine whether gene therapy is a safe and effective means of treatment.Results obtained from this project also have the potential to guide future improvements to the gene therapy protocol in order to increase HSCfunctionality after transduction.