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

点击翻译按钮获取中文摘要

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.