FreshMG is the cover story of the September 2026 issue of Nature Genetics. Our paper, Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer’s disease, examines how the brain’s resident immune cells change across aging and disease.
Donghoon Lee is first and co-corresponding author, with shared first authors James Vicari, Christian Porras and Collin Spencer. This work reflects a collaboration across computational biology, human genetics and experimental neuroscience.
A detailed view of the brain’s immune cells
FreshMG profiles 832,505 myeloid cells from 1,607 donors, resolving six subclasses and thirteen subtypes of microglia and perivascular macrophages. The atlas connects changes in cell states to aging, Alzheimer’s pathology and genetic risk.
A microglial state marked by high GPNMB expands with disease pathology and is enriched for Alzheimer’s genetic risk. Our analyses implicate MITF in maintaining this state; experiments in human and mouse models show that its protective effects depend on TREM2. These findings help connect cellular diversity to the mechanisms of disease.
The science behind the cover
Donghoon created the cover artwork to reflect the fluid transitions between myeloid cell states. Like ink blooming through water, the colors flow into one another while retaining distinct forms—a visual expression of cellular plasticity.
Seeing this work on the cover is especially meaningful for the lab: it recognizes both the biological discovery and the contributions of our graduate student co-first authors.