Characterisation of fate choice regulators in single mouse haematopoietic stem cells (360G-Wellcome-105374_Z_14_A)

Virtually nothing is known about the exact molecules responsible for orchestrating haematopoietic stem cell (HSC) self-renewal and lineage differentiation. Identifying molecules governing stem cell self-renewaland differentiation will not only provide a greater insight into stem cell biology but may also uncover novel therapeutic targets for cancer since cellular mechanisms regulating clonal expansion in cancer are likely analogous to those operating in stem cells. My PhD will focus on the identification and assessment of molecular drivers of stem cell fate choice and has two aims: 1) Identification of genes directing lineage choice in HSCs. Two approaches will be taken to identify candidates: i) Clustering of single HSC gene expression profiles and functional transplantation outcomes based on cell surface marker expression, allowing the correlation of functional outcome with a particular gene expression profile. ii) Gene expression profiling of single HSCs and their direct progeny in conditions which support either self-renewal or promote differentiation. 2) Functional validation of gene candidates in vitro and in vivo with respect to effects on self-renewal and differentiation. This will be achieved by perturbing gene function and by performing a series of single cell functional assays.