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.
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.
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.
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.
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.
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.
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.
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.
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.
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/…
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/…