New paper from my lab and @jshendure.bsky.social lab! Led by the brilliant @zukailiu.bsky.social and @cxqiu.bsky.social. We tackled how anterior and posterior progenitor cells cooperate to self-organize into an embryonic structure (termed AP-gastruloid). (1/n) www.biorxiv.org/content/10.1...

Hugely thankful for this 🙏. We will do our best to make the most of it. @erc.europa.eu!

Our latest research is out today on ‪@medrxivpreprint.bsky.social: www.medrxiv.org/content/10.1... Saturation genome editing of BRCA1 across cell types accurately resolves cancer risk. Led by the amazing Phoebe Dace. This one’s packed full of data, so check out the paper. Quick highlights… 🧵 1/n

Thrilled at the news of @10xgenomics.bsky.social ' acquisition of Scale Bio which I co-founded with Frank Steemers (ex-Illumina), @coletrapnell.bsky.social and Garry Nolan . Further thrilled to joining 10X Genomics as an scientific advisor and for the synergies that lie ahead!

Two new preprints from the @arjunraj.bsky.social‬ on #gastruloids. Both excellent. Exploring the relationship between macroscopic reproducibility v microscopic heterogeneity. Stunning experiments and much to think about biorxiv.org/content/earl... biorxiv.org/content/earl...

🚨 Most variant screens measure growth or abundance. What do they miss? That variants impact a spectrum of protein and cellular phenotypes. Variant in situ sequencing (VIS-seq) finds what’s missing: image cells 🔬 first, decode later, revealing multi-scale phenotypes for thousands of variants.👇 1/9

One thing that really bothers me with the new "virtual cell" terminology is that it is currently largely focused on a very narrow definition of models that can predict effects of trans perturbations (gene dosage, drugs etc) on gene expression. 1/

Lineage-resolved analysis of embryonic gene expression evolution in C. elegans and C. briggsae | Science www.science.org/doi/10.1126/... 😍

EPIGENETIC HULK READY TO SMASH AGAIN! GET IN LOSERS!

Expanding Perturb-seq-like screens to multicellular systems also increases the complexity of confounding effects. We encountered this when we perturbed all TFs in mosaic embryoid bodies (EBs) and develop a scalable solution by barcoding monoclonal individuals. 🧵 www.biorxiv.org/content/10.1...

New preprint with the Shendure lab @jshendure.bsky.social ! We apply the DNA Typewriter lineage recorder to mouse 3D gastruloids, a powerful model of early mammalian development. Led by Sam Regalado and CX Qiu @cxqiu.bsky.social : www.biorxiv.org/content/10.1... (1/13)

CloneSelect published in Nature Biotechnology @natbiotech.nature.com. This retrospective clone isolation method using CRISPR base editors is a powerful tool in broad biology. A history of Soh in the Yachie lab. www.nature.com/articles/s41...

Massively parallel jumping assay (MPJA) enables to test the jumping potential of thousands of transposons. Analysis of >160,000 Alu haplotypes identified transposition-asssociated domains. Amazing work by Navneet Matharu, Jingjing Zhao, Martin Kircher and many others. www.nature.com/articles/s41...

Very grateful to receive the Searle Scholars Award, especially during this challenging time! This support will help our lab realize our vision of genomic recording for reconstructing the mammalian cell fate decision. searlescholars.org/2025/04/14/s...

Happy to share our new review on molecular circuits for genomic recording with @chenomics.bsky.social! Here, we present our views on the remaining challenges in the field of genomic recording for reconstructing cell-fate decisions. (1/2)

I am hiring for a research technician role in my new lab at UC Irvine studying how transcription factors control cell identity. If you know any graduating undergrads or postbacs looking for a position, please spread the word! Apply by May 9 for full consideration. recruit.ap.uci.edu/JPF09594

Very proud of two new preprints from the lab: 1) CREsted: to train sequence-to-function deep learning models on scATAC-seq atlases, and use them to decipher enhancer logic and design synthetic enhancers. This has been a wonderful lab-wide collaborative effort. www.biorxiv.org/content/10.1...

‘With the current turmoil, China could surpass the U.S. in the near future,’ Nobel Prize winner David Baker warns www.wsj.com/articles/bio...

Big news: we are setting up a new non-profit organization to run bioRxiv and medRxiv. It's called openRxiv [no it's not a new preprint server; it's dedicated organization to oversee the servers] openrxiv.org 1/n

We're expediting sex designation change requests on birth certificates. People born in WA who want to change the sex designation on their birth certificate can do so by filing a request with us. . doh.wa.gov/DesignationC...

It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.

Here's a very important update from the AAMC (Association of American Medical Colleges) on the proposed cuts to NIH Indirect costs: "Every year since 2017, the annual spending bill that funds NIH has included language prohibiting the Administration from making changes to F&A cost rates" 1/2 🧪

🧬@science.org Multiplex generation and single-cell analysis of structural variants in mammalian genomes bit.ly/4hzFRMg @sudpinglay.bsky.social www.pinglay-lab.com @jshendure.bsky.social et al. @brotmanbaty.bsky.social @hhmi.bsky.social #synbio #genome

Now out in @science.org w/ @jshendure.bsky.social we present 'Genome-shuffle-seq': a method to shuffle mammalian genomes and characterize the impact of structural variants (SVs) with single-cell resolution in one experiment. www.science.org/doi/10.1126/...

This project stands together with work from @sudpinglay.bsky.social and @jshendure.bsky.social , who came up with an alternative method that includes a clever, single-cell sequencing strategy to read out the variants generated by scrambling. www.science.org/doi/10.1126/...

Lars Steinmetz and @seczmarta.bsky.social put together a wonderful perspective on these two studies. www.science.org/doi/10.1126/...

We're delighted to share our work on scrambling the human genome using prime editing, repetitive elements, and recombinases in @science.org , led by @jonaskoeppel.bsky.social , @f-raphael.bsky.social , with @proftomellis.bsky.social and George Church. www.science.org/doi/10.1126/...

Beware! AAV libraries prone to length & homology dependent chimerism! Our latest preprint, from the brilliant @jblalanne.bsky.social‬, was a true surprise as related phenomena are textbook for lentivirus (highly relevant to HIV & Perturb-seq) yet to our reading not known for AAV tinyurl.com/5amc562a

Brief PSA for the functional genomics community: if you are profiling complex libraries with >1 internal components (e.g., enhancer+barcodes in MPRAs) delivered via AAVs, be aware that there might be substantial unlinking within your libraries if you packaged as a pool! doi.org/10.1101/2025...

I started working on genetic therapies for Mendelian disease in 2000 - and in the subsequent 25 years have never seen a disease where the molecular aetiology has undergone as giant an "OH WOW" moment as this. www.cell.com/cell/fulltex...

We are happy to share our enhancer scramble story, a strategy to create hundreds of stochastic deletions, inversions, and duplications within mammalian gene regulatory regions and associate these new architectures with gene expression levels 🧵 www.biorxiv.org/content/10.1...

Massively parallel reporter assays (MPRAs) testing >680,000 sequences combined with machine learning to improve regulatory element & variant effect prediction. Amazing work by @vagar.bsky.social, Fumitaka Inoue, @jshendure.bsky.social and many others as part of ENCODE. www.nature.com/articles/s41...

Our latest: how to generate the notochord "Timely TGFβ signalling inhibition induces notochord" A thread: www.nature.com/articles/s41...

Just over a year ago, we launched the Seattle Hub for Synthetic Biology with @chanzuckerberg.bsky.social and @uwmedicine.bsky.social. #SeaSynBio is focused on developing tech that could spawn tools that observe cells and intervene to treat disease in real time. 🔗 alleninstitute.org/division/sea...

By definition, enhancers can activate from a distance. But with increased distance between enhancer and promoter, the activation drops. To study this systematically, we build a synthetic locus: www.cell.com/molecular-ce... 1/12

Excited to share our work @science.org. led by our incredible @tommyz626.bsky.social at @rockefelleruniv.bsky.social! By profiling 21 million single cells across life stages, we reveal aging as distinct, development-like transitions, with dramatic cell population changes in specific time windows!

Imagine a mouse in which all 10 billion cells keep a diary from fertilization. Imagine sentinel cells recording your experiences and sending out dispatches in the form of DNA. Here's a story I wrote about cell recorders 🧪 Gift link: nyti.ms/3Z3Mqza