Microglial exosome secretion coupled to TREM2: implications on iPSC-derived neurons

Microglia cells, the immune cells of the brain, have the ability to change their phenotype in response to extracellular stimuli, enabling them to launch an inflammatory response. The triggering receptor expressed on myeloid cells (TREM2) appears to be able to influence on the phenotype these cells can adapt. TREM2 mutations have been associated with a range of degenerative disorders, such as Alzheimer's disease and frontotemporal dementia, indicating the importance of microglia functioning. This project will use a range of TREM2 mutations to determine how mutations can influence glial exosome production. Exosomes, extracellular vesicles containing proteins, mRNA and miRNA, can be used by glial cells to communicate changes in the microenvironment to neighbouring neurons.
Using induced pluripotent stem cell-derived microglia-like cells, we will investigate exosomal secretion rate and content and the effect this could have on neuronal maturation, functioning and viability.