The Whitehall Foundation has awarded a three-year, $225,000 grant to Tristan Qingyun Li, PhD, assistant professor of neuroscience and genetics. The funding will go to investigate the function of microglia, immune cells that reside in the brain and perform myriad critical functions during development, injury and disease.
Microglia were once thought to play passive roles in responding to infection, but in the last decade, scientists have discovered that microglia are essential, active participants in brain function. During development, for instance, they trim neurons’ excess synapses—the connections between cells that allow them to communicate to one another—and direct proper vascularization so the brain has sufficient blood flow in the right places.
“Because microglia play so many different roles, the big question is, are all these microglia the same—meaning, they are multitaskers doing many things—or is there a division of labor?” said Li, who maintains affiliations with the Hope Center for Neurological Disorders and the Center for Neuroimmunology and Neuroinfectious Diseases at the School of Medicine. It turns out that the latter is true; subsets of microglia appear to have specialized functions.
Li’s lab is dissecting precisely which activities are performed by which subsets of microglia. During his postdoctoral work at Stanford University, Li conducted single-cell RNA sequencing on the mouse brain and discovered one subset of microglia that existed for a short period of time about a week after birth only in the white matter tract of the brain. This cell type, called proliferative-region-associated microglia, or PAM, had a distinct gene expression profile and was effective at eliminating cells called oligodendrocytes that were dying as part of a typical developmental process.
Support from the Whitehall Foundation will advance studies on the function of PAM in development, disease and behavior.
The bottom panel is a 3-D reconstruction of a PAM cell (green) engulfing a nucleus (blue). The arrow points to the PAM cell’s nucleus.
Figures from: Li Q et al. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron. 2019; 101(2): 207-223.e10.