Longevity & AgingHuman Brain Cell Triple Culture Reveals Astrocytes Drive Microglial Disease State
Researchers at Brigham and Women's Hospital developed a reproducible human iPSC-derived triple culture (triculture) system combining neurons, astrocytes, and microglia to study brain cell communication in health and Alzheimer's disease. Using single-cell RNA sequencing and protein analysis, they found that co-culturing all three cell types dramatically changes each cell's behavior. Most strikingly, astrocytes drive microglia into a disease-associated microglia (DAM) state—marked by elevated TREM2, APOE, SPP1, and GPNMB—even without overt pathological stimuli. Paradoxically, when neurons carrying familial Alzheimer's disease mutations were introduced, this astrocyte-driven DAM signature was significantly suppressed, despite triggering a separate inflammatory response. The model is operational within 20 days of thawing cryopreserved cells, making it broadly accessible for neurodegeneration research.
