Chromatic topological mapping reveals organelle-specific spatial organization within microglia

Abstract

In branched cells, including neurons and glia, intracellular organelles are distributed across complex cellular arbors where their spatial arrangement supports transport, signaling, and compartmentalized function. Although intracellular organelle organization is increasingly recognized as an important feature of cellular state and function, existing approaches assess organelle abundance or spatial position without accounting for the branching architecture that shapes cellular function. Here, we introduce the chromatic topological morphology descriptor (chromatic TMD), a framework that quantitatively resolves intracellular organization in relation to branching morphology. Applied to reconstructed microglia with annotated lysosomal and mitochondrial compartments across retinal layers and after optic nerve crush injury, chromatic TMD identifies distinct organelle-specific spatial programs: CD68+-endosomal-lysosomes undergo layer-dependent branch-specific redistribution, revealing selective intracellular reorganization after injury, whereas mitochondrial organization remains closely coupled to branching morphology. These findings establish intracellular organization as an additional layer of cellular architecture that can be systematically analyzed across branched neural cells.