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Dupre, J.-S.

Publications and source records attributed to Dupre, J.-S..

2 recordsLinked to original sources

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 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.

neuroscience↗

High-throughput histopathology for complex in vitro models

Human complex in vitro models (CIVMs) have demonstrated remarkable potential to study tissue development, physiology and disease at high-throughput. To effectively employ these miniaturized systems in translational preclinical research, their in-depth benchmarking is pivotal. Histology has been the core of tissue characterization for centuries and the foundation of spatial phenotyping. However, standard histology workflows are inherently low-throughput and centered on large tissue pieces. This does not match the high sample volumes and small sample sizes in CIVM research. Here, we introduce a holistic histo-workflow, utilizing 3D-printed histomolds that facilitate co-planar embedding of CIVMs at high-throughput, resulting in up to 48 samples in one section. We developed a variety of model-specific histomold designs that enable spatially controlled histological sectioning and downstream analyses. We describe these workflows, including mold generation, highplex staining and image analysis, and exemplify their application to histological analyses of various CIVMs. Altogether, the histomolds introduced here afford opportunities for CIVM processing and analysis, while significantly reducing labor and reagent resources, thereby democratizing high-throughput CIVM in histopathology.

pathology↗