Human microglia in brain assembloids display region-specific diversity and respond to hyperexcitable neurons carrying <i>SCN2A</i> mutation.

ABSTRACT: Microglia critically shape neuronal circuit development and function, yet their region-specific properties and roles in distinct circuits of the human brain remain poorly understood. In this study, we generated region-specific brain organoids (cortical, striatal, and midbrain), each integrated with human microglia, to fill this critical gap. Single-cell RNA sequencing uncovered six distinct microglial subtypes exhibiting unique regional signatures, including a subtype highly enriched for the GABA_B receptor gene within striatal organoids. To investigate the contributions of microglia to neural circuitry, we created microglia-incorporated midbrain-striatal assembloids, modeling a core circuit node for many neuropsychiatric disorders, including autism. Using chemogenetics to activa

SUBMITTER: Wu J 

PROVIDER: S-EPMC12915608 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature