Microglial heterogeneity: influence of human 2D, 3D, and co-culture models on gene expression and immune function.

ABSTRACT: Microglia, the resident immune cells of the central nervous system, exhibit substantial phenotypic and functional diversity shaped by local microenvironmental cues. While advanced in vitro human microglial models exist, the influence of culture dimensionality and cellular context on microglial state composition remains poorly defined. Here, we analyzed single-cell RNA sequencing datasets from human monocyte-derived microglia (MDMi) cultured under two-dimensional (2D) and three-dimensional (3D) monoculture, as well as 3D neural-glial co-culture conditions. Across platforms, four microglial states were identified, including interferon (IFN)-responsive, chemokine-enriched, metabolically active, and proliferative states, with pronounced environment-dependent transcriptional shifts. 2D c

SUBMITTER: Etebar F 

PROVIDER: S-EPMC12932485 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature