Xiaowei Zhuang's Lab at Harvard University and Howard Hughes Medical Institute

Cambridge, MA 02138
Excited to share our recent paper (doi.org/10.1016/j.cell.2026.…)! In this multi-year effort, we developed RT&T-AMP-MERFISH, enabling whole-transcriptome-scale, isoform-resolved single-cell spatial transcriptomics and imaging ~33,000 RNAs in the brain.
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RT&T-AMP-MERFISH opens new ways to study tissues at whole-transcriptome-scale with high spatial resolution, revealing how transcript diversity, gene and isoform regulation, and cell-cell interactions contribute tissue function in health and disease.
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These data further revealed brain structures with especially rich isoform specificity. For example, the choroid plexus and hippocampus showed specific or preferential isoform expression across many genes.
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Our isoform-resolved single-cell spatial transcriptomics data revealed widespread spatial and cell-type-specific isoform usage across the brain, with many genes showing distinct isoform enrichment in different anatomical regions and/or cell types.
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Our whole-transcriptome-scale imaging data revealed spatially organized gene programs, cell-type- and region-specific differential expression, and ligand-receptor-based cell-cell communication patterns across the brain.
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Integrating RT&T-AMP with multiplexed error-robust fluorescence in situ hybridization, (MERFISH), we imaged ~23,000 genes and ~10,000 isoforms in single cells in brain tissues with high spatial resolution.
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We developed an in situ RNA amplification method, RT&T-AMP, that uses reverse transcription followed by transcription to generate amplicons at original transcript sites with uniform transcript body coverage, enabling to imaging of short RNA sequences anywhere along transcripts.
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What is the global structure of cell-state space—and how do perturbations drive transitions within it? Excited to share our new preprint (biorxiv.org/content/10.64898…), a work in collaboration with @JswLab.
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Moreover, we perform a genome-scale Perturb-seq screen in human embryonic stem cells, validating and extending these findings and uncovering a class of mesenchymal transitions induced by diverse perturbations to cellular stress-response pathways.
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Explore the Global Pattern Browser: xingjiepan.github.io/SCMG/ Code: github.com/xingjiepan/SCMG
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Delighted to share this preprint from Prof. Rong Fan Lab @RongFan8 and Prof. Sidi Chen lab @sidichen on Spatially Resolved in vivo CRISPR Screen Sequencing via Perturb-DBiT. Congatulations, Alev, Xiaolong, Feifei, Paul, Sidi and Rong!
Thrilled to share Perturb-DBiT — spatial unbiased in vivo perturb-seq with genome-scale CRISPR libraries! Hope you enjoy reading it over the Thanksgiving week 🥰 Kudos to @AlevBaysoy, Xiaolong, Feifei, and Paul. & collaboration with @sidichen, Hongbo Chi. biorxiv.org/content/10.1101/…
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Check out our preprint on Perturb-multi (doi.org/10.1101/2024.11.18.6…), a multi-year collaborative effort that enabled multi-modal in vivo genotype-phenotype mapping by pooled genetic perturbations and high-dimensionality phenotype readout by imaging and sequencing.
In collaboration with Reuben Saunders, @JswLab, and Xiaowei Zhuang, we are very excited to release Perturb-Multi: a platform for pooled multimodal genetic screens in intact mammalian tissue. Check it out! biorxiv.org/content/10.1101/…
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