Grant: CIHR Fellowship

Haematopoietic stem cells (HSCs) are specialized stem cells (SCs) that give rise to the blood and immune cells. First HSCs emerge during the embryogenesis. These new HSCs have a higher ability for proliferation and differentiation into different cell types than the adult HSCs, suggesting that their environment influences their fate. Previous studies showed that SCs reside in small niche environment. Such environments provide a special setting for cell-cell communication, extracellular matrix construction, and control of signalling between the cells. Yet, genes/pathways and expression profile of individual cells within the human embryonic HSCs niches remain poorly understood. Our current inability to generate bona fide human HSCs from pluripotent stem cells (PSCs) suggests that these HSCs derived in vitro may have different gene expression profile than the ones developed in embryos due to different stem cell niche environments. Studying these niche environments was difficult until the recent development of the Fluorescent In Situ Sequencing (FISSEQ) by the Church lab. FISSEQ enables single-cell transcriptome sequencing of fixed, intact tissue samples. Subsequent development of a modified version of FISSEQ called targeted FISSEQ (tFISSEQ) allows detection of small RNAs and even proteins by FISSEQ. These technologies, for the very first time, enable us to evaluate the gene expression landscape of SCs and all other cells in the SCs niche, in the context of their native spatial environment. Human PSCs-derived teratoma engrafted in immunodeficient mice, develops HSCs that possess good repopulation ability in secondary recipient mice. This could be a faithful model that represents at least in part the heamogenic emergence process in the embryo. Using tFISSEQ to obtain spatial expression landscape of proteins and miRNAs in the teratoma and PSC-to-HSCs in vitro models will finally shed light on the key effectors and pathways in heamogenic development in human embryos.