An in vivo brain organoid platform reveals how human neurons and glia interact across development, aging, and disease. Fred H. Gage, Ph.D., generates three dimensional organoids from induced pluripotent stem cells and examines their maturation, synapses, and network activity with two-photon imaging and single-cell profiling. Gage integrates human microglia and astrocytes to study immune signaling, injury responses, and support functions that shape circuit behavior. Transplantation enables vascularization, reduces cell death, and yields features consistent with a blood brain barrier. Analyses identify diverse astrocyte types and trajectories, while patterns of tau expression inform Alzheimer’s disease modeling. Gage also converts adult fibroblasts into age retaining neurons that assemble into 3D spheroids, creating complementary models to connect genes, cells, and circuits with pathology and to guide strategies for prevention and therapy. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 41160]