Studying blood stem cell development through single cell and lineage tracing analyses

Supervisor:  Prof Catherine Porcher

Understanding the molecular mechanisms underlying cell fate decisions during embryonic development is a key biological question, not only from a fundamental scientific point of view but also to inform attempts at producing tissue stem cells in vitro for regenerative medicine purposes. The Porcher lab investigates how blood (haematopoietic) stem cells (HSCs) are specified during embryonic development.  We have recently shown that multilineage-primed mesodermal cells acquire a blood fate at the expense of other mesodermal-derived lineages (heart, bones or muscles) through tight transcriptional and epigenetic control of gene expression. There is now increasing evidence that the earliest events underlying lineage specification arise before mesoderm patterning, i.e. before gastrulation. The PhD student will join our team to dissect the very first molecular events controlling haemopoietic specification during embryonic development at the epiblast stage. Single cell analyses and lineage tracing studies will be developed to track the earliest cells programmed to give rise to the HSC lineage, using in vivo mouse models as well as human and mouse embryonic stem (ES) cell systems. Transcriptomics, functional and biochemical approaches will further characterise the networks of genetic and protein/protein interactions required to establish a haematopoietic-specific gene expression programme and drive HSC development. This study will provide general principles in the control of cell fate decisions and guide the design of protocols supporting HSC differentiation in vitro from pluripotent stem cells.

The host laboratory is based in the MRC Molecular Haematology Unit. This project is an excellent opportunity to be part of a vibrant scientific community and to acquire research skills in state-of-the-art molecular and cellular technologies (such as ES cell differentiation cultures, single cell genomics, genome editing (CRISPR/Cas9), lineage tracing techniques, chromatin immunoprecipitation (ChIP), next generation sequencing, flow cytometry). Our Institute holds regular seminar series and organises formal training in many essential skills (such as bioinformatics) as well as a methods and techniques course for all first year PhD students. As part of the MHU student mentoring scheme, students have a Thesis Committee to advise them on their academic work. Finally, students are strongly encouraged to attend national and international meetings and present their work.

For further information, please contact Prof Catherine Porcher