In this recent Nature Methods Perspective, I outline how tissue clearing, spatial-omics, and AI converge to create deep 3D histology, enabling unbiased, organism-scale biology and next-generation digital pathology. www.nature.com/articles/s41...
13.02.2026 10:34 โ
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A new preprint introduces aDISCO, a DISCO-based clearing approach that makes whole archival FFPE human tissues transparent and antibody-compatible, enabling true 3D light-sheet histology across brain & multiple organs at cellular resolution. Aguzzi & Helmchen teams.
www.biorxiv.org/content/10.1...
08.02.2026 19:41 โ
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This is going to be fun! I promise!
29.12.2025 20:51 โ
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Most transcriptomics studies sample ~0.001% of a mouse. Which region do we choose? Often: we guess.
Meet DISCO-seq ๐ค flipping the order: RNA-preserving clearing โ whole-organ/whole-body 3D imaging โ pick ROIs in 3D โ unbiased scRNA-seq.
Preprint: www.biorxiv.org/content/10.6...
18.12.2025 14:44 โ
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Single cell transcriptomics from cleared tissue? Impossible you say? Check out our latest preprint!
23.12.2025 10:14 โ
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โจ DISCO-seq bridges 3D anatomy and single-cell genomics.
Unbiased, imaging-guided, whole-organ transcriptomicsโfrom brain tumors to infection biology.
18.12.2025 14:44 โ
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Take-home: most spatial biology still starts from 2D slices + predefined ROIs/genes.
DISCO-seq changes the paradigm: whole-organ/whole-body 3D first โ unbiased single-cell transcriptomics second.
18.12.2025 14:44 โ
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Spike S1 induces region- and condition-specific gene programs, highlighting spatial immune specialization along the gut.
18.12.2025 14:44 โ
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Small intestine scRNA-seq preserves cell-type diversity across conditions/regions (PBS vs S1; duodenum vs ileum) with expected epithelial, immune, and stromal populations.
18.12.2025 14:44 โ
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Whole-body application: 3D DISCO imaging maps organ-specific SARS-CoV-2 Spike S1 tropism.
In the gut, we see distinct enrichment patterns (duodenum vs ileum), enabling unbiased ROI selection.
18.12.2025 14:44 โ
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DISCO-seq resolves region- and cell-type-specific programs in GBM: neurons and microglia show distinct states across core vs remote niches.
18.12.2025 14:44 โ
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Imaging-guided ROI selection enables spatially resolved transcriptomics: tumor core vs remote rostral/caudal ROIs within the intact brain.
18.12.2025 14:44 โ
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3D quantification maps tumor burden across annotated brain regions, distinguishing small blobs, clusters, and large lesionsโrevealing region-specific heterogeneity
18.12.2025 14:44 โ
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Glioblastoma: whole-brain 3D imaging reveals dissemination beyond the primary lesion.
Satellite tumors + contralateral spread become visible in 3Dโoften missed in 2D or standard clinical imaging.
18.12.2025 14:44 โ
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Workflow in one line:
RNA-preserving clearing โ probe hybridization & partitioning โ library construction โ sequencing โ analysis.
Cell-type composition and gene detection are well preserved.
18.12.2025 14:44 โ
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Platform-agnostic: strong libraries across technologies (single cells and nuclei).
Decrosslinking is criticalโmarkedly improves fragment size and library quality.
18.12.2025 14:44 โ
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Key challenge: solvent-based clearing usually destroys RNA.
DISCO-seq systematically optimized clearing chemistries (THF/DCM + controlled rehydration) to preserve RNA integrity comparable to fresh/fixed tissue.
18.12.2025 14:44 โ
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Spatial methods often rely on thin sections or predefined gene panels.
DISCO-seq keeps the global 3D context and lets you select ROIs anatomicallyโthen profile them at single-cell resolution.
18.12.2025 14:44 โ
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Most transcriptomics studies sample ~0.001% of a mouse. Which region do we choose? Often: we guess.
Meet DISCO-seq ๐ค flipping the order: RNA-preserving clearing โ whole-organ/whole-body 3D imaging โ pick ROIs in 3D โ unbiased scRNA-seq.
Preprint: www.biorxiv.org/content/10.6...
18.12.2025 14:44 โ
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Congratulations to our scientist, Laurent Simons, for earning his PhD in quantum physics at just 15โan exceptional achievement.
In our lab, Laurentโs work focuses on in silico biology to accelerate treatment of devastating diseases. Weโre thrilled to have him on the team.
08.12.2025 14:22 โ
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Be your own advocate. Share your preprint on social media. Write a short thread explaining the key findings. If you're not at a top-tier institution, you have to be even more proactive. Create your own audience. It shows confidence and initiative.
09.11.2025 20:08 โ
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Post to a preprint server (e.g., bioRxiv). The fear of being scooped is mostly a myth now. A preprint plants your flag, establishes priority, and gets your work seen by reviewers in your field early. Itโs free advertising.
09.11.2025 20:08 โ
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Finally, don't wait for publication day to create visibility. The work starts months earlier.
09.11.2025 20:08 โ
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"We developed a method to do X, which for the first time allows us to solve problem Y." No jargon.
Focus on the Story, Not Just Data: Editors are looking for a compelling narrative along with great science. What is the problem? What was the breakthrough? Why does it matter to a broad audience?
09.11.2025 20:08 โ
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Also, master your pitch!
Once you get that face-to-face meeting, you have about 60 seconds to make an impact. Don't waste it.
Nail the One-Liner: Start with a single, clear sentence that states your main finding and its importance.
09.11.2025 20:08 โ
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Don't just do great science and hope it gets noticed. Be strategic, be human, and actively create your opportunities.
What else would you suggest to the young generation that their papers get published well?
09.11.2025 20:08 โ
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