Unravelling the clonal nature of microglial diversity in the brain

Skills Priority Alignment: Quantitative Biology

Microglia, the brain's resident macrophages, have key roles in brain development and function, in health and disease. Microglia are developmentally derived from the yolk sac, a distinct origin and lineage from the majority of other tissue-resident macrophages. After a few progenitors colonize the brain, the population undergoes massive expansion, achieving the adult density shortly after birth. This process suggests the generation of a limited number of subpopulations of cells with potentially diverse properties.

In this project we will use a cutting-edge toolbox to label and fate-map yolk sac derived cells with multicolour transgenic and viral approaches, combined with the analysis of the transcriptional profile at the single-cell level, using bespoke microfluiding technologies. This setup will allow the study of our hypothesis: the microglial population is composed by a limited number of subpopulations, dictated from development, defining regional and functional heterogeneity. Insights into the composition of the microglial population will inform on the roles of these cells in the healthy and diseased brain, with particular relevance for age-related neurological disorders.