A perturbation atlas of mouse neural organoids resolves macroglial reactivity and nominates drivers of degeneration
Understanding neuro-glial roles in homeostasis and disease requires scalable central nervous system (CNS) models, particularly as macroglia like astrocytes and Muller glia remain challenging to study in slow-developing human systems. Here, we generate and map the cellular diversity of mouse neural organoids spanning multiple brain regions and the retina. Benchmarking transcriptomic maturation…
Researchers have created a detailed map of macroglial reactivity in mouse neural organoids to better understand glial roles in brain health and disease. These organoids, which replicate brain tissue, were developed to study macroglia, such as astrocytes and Muller glia, which are difficult to investigate in slower-developing human systems. By benchmarking the transcriptomic maturation of these organoids against in vivo references, the researchers captured the postnatal neuro-macroglial states within a month.
The study revealed that macroglia are highly sensitive to inflammatory signals and adopt specific transcriptomic states that are also observed in vivo. Using a single-cell perturbation screen targeting 13 Muller-glia-specific pathways, the researchers were able to map the effects of particular inflammatory cytokines on degeneration-like stress programs in photoreceptors and distinct reactive states in Muller glia. One such response was driven by Oncostatin M, leading to a chaperone-associated state in these glial cells.
Mechanistically, the study identified gp130-STAT3 signaling as a potential target for reducing macroglial reactivity and protecting photoreceptors from distress. These single-cell atlases now serve as a foundation for exploring cellular interactions and glial pathology in the mature central nervous system.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
