A perturbation atlas of mouse neural organoids resolves macroglial reactivity and nominates drivers of…

Abstract

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 against in vivo references captures postnatal neuro-macroglial states within a month. We show that macroglia are highly responsive to inflammatory cues and adopt specific transcriptomic states also found in vivo. Through a single-cell perturbation screen targeting 13 Muller-glia-specific pathways, we map how certain inflammatory cytokines drive degeneration-like stress programs in photoreceptors and distinct reactive states in Muller glia, including an Oncostatin M-driven chaperone-associated state. Mechanistically, we identify gp130-STAT3 signaling as a targetable driver of macroglial reactivity and photoreceptor distress. Together, these single-cell atlases provide a foundation for dissecting cellular crosstalk and neuro-glial pathology in the mature CNS.

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BibTeX RIS

BibTeX

@misc{dupre2026perturbation,
  title = {{A perturbation atlas of mouse neural organoids resolves macroglial reactivity and nominates drivers of degeneration}},
  author = {J.-S. Dupre and M. Signer and J. Rao and L. Adam and L. Gaspa-Toneu and M. Almato-Bellavista and I. Cubela and L. Sadiraj and T. Fuhrer and J. Scherer and T. Pares i Borell and M. Schröter and A. Hierlemann and M. Zampieri and M. Lutolf and J. G. Camp},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.09.757894},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757894v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - A perturbation atlas of mouse neural organoids resolves macroglial reactivity and nominates drivers of degeneration
AU  - J.-S. Dupre
AU  - M. Signer
AU  - J. Rao
AU  - L. Adam
AU  - L. Gaspa-Toneu
AU  - M. Almato-Bellavista
AU  - I. Cubela
AU  - L. Sadiraj
AU  - T. Fuhrer
AU  - J. Scherer
AU  - T. Pares i Borell
AU  - M. Schröter
AU  - A. Hierlemann
AU  - M. Zampieri
AU  - M. Lutolf
AU  - J. G. Camp
PY  - 2026
DA  - 2026/10/09
PB  - bioRxiv
DO  - 10.64898/2026.10.09.757894
UR  - https://www.biorxiv.org/content/10.64898/2026.10.09.757894v1
AB  - 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 against in vivo references captures postnatal neuro-macroglial states within a month. We show that macroglia are highly responsive to inflammatory cues and adopt specific transcriptomic states also found in vivo. Through a single-cell perturbation screen targeting 13 Muller-glia-specific pathways, we map how certain inflammatory cytokines drive degeneration-like stress programs in photoreceptors and distinct reactive states in Muller glia, including an Oncostatin M-driven chaperone-associated state. Mechanistically, we identify gp130-STAT3 signaling as a targetable driver of macroglial reactivity and photoreceptor distress. Together, these single-cell atlases provide a foundation for dissecting cellular crosstalk and neuro-glial pathology in the mature CNS.
ER  -

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