Wellcome Trust PhD Programme in Mathematical Genomics and Medicine. (360G-Wellcome-102273_Z_13_Z)

Haematopoiesis occurs in two distinct waves during development, namely transient primitive haematopoiesis and definitive haematopoiesis that persists into adulthood. Many important questions remain unanswered about the earliest stages of blood development. For example, there are debates on the identity of the ini tial early mesodermal cells that give rise to the H SCs, as well as the factors that regu late the cell fate decisions in these cells. In this project, t seek to provide answers to these questions by utilising recently devel.oped techniques (i.e. single-cell RNAseq [scRNAseq] and single-molecule RNA in situ hybridisation(smRNAISH]) to study haematopoiesis in mouse embryos. Analysis at single cell resolution has the potential to resolve many of the current con troversies on the nature of early blood development. Firstly, I propose to identify subpopulations present in wild type early mesodermal cells using scRNAseq data. Once the sub populations are identified, their spatiotemporal trajectories will be analysed using smRNA ISH . Both scRNAseq and smRNA ISH will then be performed on mutant mice with key transcription factor knockout to observe how the knockouts affect normal haematopoiesis. Finally, I propose to synthesise a transcriptional regulatory network by incorporating all the information obtained from scRNAseq and smRNA ISH .