Ochoa Zermeno, S. | Search bioRxiv

bioRxiv2026

The Microglia Forebrain Assembloid Model Recapitulates Human Brain Development and Neuroimmune Biology.

Microglia are innate immune cells of the CNS whose dysfunction contributes to inflammation and metabolic changes across neurodegenerative and CNS disorders. Across all stages of life, microglia are essential for immune surveillance, neural homeostasis, and synaptic pruning; however, their role in neurodevelopment is less understood. Microglia invade the brain during early neurogenesis, prior to neuronal/glial differentiation, but their potential role at this stage remains undescribed. To model neuroimmune interactions during human cortical development, we created an "assembloid" of human ESC-derived forebrain organoids combined with developmentally matched microglia during cortex formation. Functional contributions of microglia were compared to control organoids using histology and metabolomics.

neuroscience↗

bioRxiv2026

Representation Methods of Transcriptomics with Applications in Neuroimmune Biology

Interpretable representations of gene expression are used to define cellular identities and the molecular programs active within cells, two related, but distinct phenomena. In the case of microglia, a cell type with high transcriptomic, functional, and morphological heterogeneity, the predominant representation of transcriptomic data presumes the adoption of distinct molecular identities, despite a lack of easily separable transcriptional states. Here, we explore alternative transcriptomic representations by comparing two single-cell analysis methods: differential expression analysis for identities and co-expression network analysis for molecular programs. For microglia, co-expression network analysis identifies highly significant functional ontologies not resolved by differential expression analysis. The identified co-expression modules are preserved across transcriptomic datasets and suggest reducible functional programs that activate and modulate depending on context. We conclude that co-expression analysis constitutes a best practice for single cell analysis of an individual cell type and describing microglia function as concurrent molecular programs offers a more parsimonious model of microglia function.

bioinformatics↗