PhD candidate The University of Hong Kong Hong Kong Island, Hong Kong
Abstract: Human pluripotent stem cells (hPSCs) have been considered a promising source for the generation of immune cells for immunotherapy and transplantation. However, lympho-myeloid hematopoiesis has been masked by the dominant primitive and myeloid-restricted waves of hematopoiesis in hPSC differentiation. Generating functional immune cells remains a great challenge. Among them, T cells and natural killer (NK) cells are of special interest due to their substantial potential in immunotherapy. T cells play a critical role in adaptive immunity while natural killer (NK) cells are important for the innate immune system. By knocking out a key T cell regulator gene Bcl11b, T cells can acquire NK features, termed induced-T-to-NK (ITNK) cells, which are highly potent in tumor killing. We establish an efficient, highly reproducible and cell line-independent system for human embryonic hematopoiesis and develop a method to generate ITNK cells from human expanded potential stem cells, which can be further engineered for antitumor functions. Our human EPSC-based hematopoiesis system can in a week produce a large number of CD34+ hematopoietic stem/progenitor cells, which process multilineage potentials. The HSPCs can differentiate to T/ITNK cells robustly, serving as a novel type of cell source for cell-based cancer therapy. Human EPSCs are genetically and epigenetically stable and are amenable to efficient precision genome editing. Our human EPSC-based hematopoiesis system can thus offer a useful tool to genetically dissect human hematopoiesis.
Funding Source: This project is supported by Health@InnoHK, Innovation Technology Commission, HKSAR
