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Siyuan (Steven) Wang @sstevenwang.bsky.social · 20h

Link to Yale News article about this work: news.yale.edu/2025/10/02/n...

New technique offers bigger and better window into RNA activity in complex tissue

Yale researchers have created a new tool that will enable researchers to better view how RNA molecules function in tissue space.

news.yale.edu

Siyuan (Steven) Wang @sstevenwang.bsky.social · 20h

Check out our new RAEFISH spatial transcriptomics technology published in Cell! This work represents the first time that transcripts from more than 20,000 genes were directly imaged in situ with any technology, and the first time numerous gRNAs were directly probed in an image-based CRISPR screen.

Cell - a Cell Press journal @cp-cell.bsky.social · 7d

Now online! Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution

Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution

RAEFISH delivers whole-transcriptome (>20,000 genes) imaging at single-molecule resolution in cells and tissues and enables direct gRNA detection for high-content, image-based CRISPR screens.

dlvr.it

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Reposted by Siyuan (Steven) Wang

GenomeTDCC @genometdcc.org · 7d

New highlight video! 🧪🧬💻
RAEFISH from Steven Wang at Yale unlocks whole-transcriptome imaging at single-molecule resolution. See 20,000+ RNAs light up in cells and tissues. Plus get direct gRNA detection in high-content CRISPR screens. Spatial biology just leveled up

www.youtube.com/watch?v=P2j6...

Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution

YouTube video by GenomeTDCC

www.youtube.com

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Reposted by Siyuan (Steven) Wang

Nature Genetics @natgenet.nature.com · Aug 27

🎉PUBLISHED @natgenet.nature.com

📰Tracing the evolution of single-cell 3D genomes in Kras-driven #cancers.

By Miao Liu, @muzumdarlab.bsky.social, @sstevenwang.bsky.social and colleagues.

⬇️

www.nature.com/articles/s41...

Tracing the evolution of single-cell 3D genomes in Kras-driven cancers - Nature Genetics

This study uses chromatin tracing to identify alterations in single-cell 3D genome conformation during the progression of Kras-driven mouse lung adenocarcinoma and pancreatic ductal adenocarcinoma, an...

www.nature.com

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Reposted by Siyuan (Steven) Wang

Yale Cancer Center @yalecancer.bsky.social · Aug 19

New @natgenet.nature.com study from @muzumdarlab.bsky.social + @sstevenwang.bsky.social
maps 3D genomes in KRAS-driven lung & pancreatic #cancer, revealing stage-specific changes + potential biomarkers.

➡️ yalecancercenter.org/news-article...

Cancer's Progress Detailed by 3D Genomic Maps

Using new technology, Yale researchers examine cancer progression in single cells to visualize and understand its evolution from pre-cancerous to advanced

yalecancercenter.org

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

Such a pleasure collaborating with you and your lab too, Mandar! Cheers!

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

Link to YSM News article about this work: medicine.yale.edu/news-article... 12/12

Cancer's Progress Detailed by 3D Genomic Maps

Using new technology, Yale researchers examine cancer progression in single cells to visualize and understand its evolution from pre-cancerous to advanced

medicine.yale.edu

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

Link to paper: www.nature.com/articles/s41... 11/12

Tracing the evolution of single-cell 3D genomes in Kras-driven cancers - Nature Genetics

This study uses chromatin tracing to identify alterations in single-cell 3D genome conformation during the progression of Kras-driven mouse lung adenocarcinoma and pancreatic ductal adenocarcinoma, an...

www.nature.com

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

This work was done in collaboration with my @yaleschoolofmed.bsky.social colleague Professor Mandar Muzumdar @muzumdarlab.bsky.social and co-led by Drs. Miao Liu, Shengyan Jin, and Sherry Agabiti. Congrats to all authors! Also thank you National Cancer Institute for funding this work! 10/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

We expect that applying these approaches broadly will have an enormous impact on understanding the epigenetic basis of cancer in situ and will lead to the development of novel diagnostic, prognostic, and therapeutic biomarkers based on the 3D genome. 9/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

Our work also establishes a series of experimental and analytic methodologies (e.g., Trace2State, Trace2Biomarker, Trace2Regulator), allowing adaptation of these pipelines by the research community to study many other types of cancer and biological systems. 8/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

Overall, our work charts a comprehensive blueprint of 3D genome alterations during cancer progression in the native tissue context and systematically demonstrates how this rich resource can provide novel biological insights and potential biomarkers. 7/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

4) A new way to discover novel 3D genome regulatory genes in cancer, which can also serve as potential therapeutic targets. 6/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

3) A new 3D genome function, as our data reveal that cancer genes associated with 3D compartment changes are more stably regulated than non-compartment-regulated genes. 5/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

2) The utility of 3D genome mapping in better discovering prognostic and predictive biomarkers – uncovering novel candidate progression driver genes associated with patient survival as potential therapeutic targets. 4/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

1) Surprisingly nonmonotonic, stage-specific alterations in global 3D genome folding heterogeneity, compactness, and compartmentalization as cancers progress from normal to preinvasive to invasive tumors, elucidating an unexpected 3D genome structural bottleneck during early cancer progression. 3/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

Particularly, we further developed a single-cell, genome-wide chromatin tracing method for applications to lung, pancreas, and cancer tissues. We applied our method to faithful autochthonous murine models of lung and pancreatic cancers that mimic the cognate human cancers. Our data revealed: 2/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 19

Glad to share our latest publication in Nature Genetics: Tracing the evolution of single-cell 3D genomes in Kras-driven cancers. In this work, we generated the first single-cell 3D genome atlases of any cancer using any technique. 1/12

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 9

Check out this new video highlighting our lab :-) Thank you @yaleschoolofmed.bsky.social Video Team for the production! m.youtube.com/watch?v=p-hE...

Genome Architectures & Spatial Transcriptomics - The Siyuan Wang Lab at Yale School of Medicine

YouTube video by Yale Medicine

m.youtube.com

Siyuan (Steven) Wang @sstevenwang.bsky.social · Aug 8

Thank you @genometdcc.bsky.social and the National Human Genome Research Institute for inviting me to present this introductory lecture to the public at the Genomic Technologies Open Science Day 2025!

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Reposted by Siyuan (Steven) Wang

GenomeTDCC @genometdcc.org · Jul 30

How does 6ft of #DNA fit inside a cell only 10 microns wide?

@sstevenwang.bsky.social provides a brief history of contemporary 3D #genomics technologies. Learn how spatial organization of DNA plays a vital role in gene regulation, development, and disease. 🧬🖥️🧪 #STS
www.youtube.com/watch?v=gXCO...

A Brief History of Contemporary 3D Genomics Technologies

YouTube video by GenomeTDCC

www.youtube.com

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Reposted by Siyuan (Steven) Wang

Siyuan (Steven) Wang @sstevenwang.bsky.social · Jun 26

Introducing Epi-PHR, the first non-disruptive, high-genomic-resolution, image-based epigenetic profiling method. Allelic Epi-PHR generates the first single-cell phased examination of histone mark deposition and 3D genome architecture at an imprinted locus by any technique. 1/8

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Jun 26

We expect Epi-PHR will find broad application in diverse biological and medical contexts. Link to our preprint: www.biorxiv.org/content/10.1... 8/8

https://biorxiv.org/content/10.110…

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Jun 26

Surprisingly, we found among the maternal copies of this locus, the relationship between the histone mark and a chromatin domain boundary is opposite to what one would expect. This surprising finding was uniquely enabled by Epi-PHR. 7/8

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Siyuan (Steven) Wang @sstevenwang.bsky.social · Jun 26

Finally, we developed allelic Epi-PHR and combined it with fine-scale chromatin tracing to simultaneously profile histone mark deposition and chromatin folding at an imprinted genomic locus with parent-of-origin specificity. 6/8

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