Generation of Hematopoietic Stem Cells from Human Expanded Potential Stem Cells for Cell-Based Immunotherapy

Abstract:

Human hematopoietic stem cells (HSCs) possess the inherent potential to differentiate into all blood lineages. Human expanded potential stem cells (EPSCs), which can give rise to all embryonic and extra-embryonic cell lineages, provide a robust model for generating HSCs and immune cells in vitro. Our lab has established an efficient protocol for the steady induction of hematopoietic stem and progenitor cells (HSPCs) from EPSCs. These EPSC-derived HSPCs demonstrate multi-lineage potential, capable of differentiating into erythroid cells, macrophages, NK cells, and T cells. Transcriptional profiling via single-cell RNA-sequencing confirms the presence of distinct endothelial and hematopoietic clusters, validating our approach. A central challenge in this field is developing methods to promote the generation of HSCs with robust engraftment capacity and full lymphopoiesis potential. We are developing protocols to measure the EPSC-derived HSPC in vivo function using humanized mouse models. We will combine the single cell data and mouse model to improve the efficient of HSC generation from EPSC. Finally, we aim to use the protocol to generate HSC that can be used clinically.

Skills and experience required for the project:

Stem cell culture
Flow cytometry
PCR
mouse handling
R languages
Bioinformatics analysis
Team collaboration spirit