Jay Shendure

We have significantly improved the protocol for recording CRE activities and orders with ENGRAM. We also designed new plasmids for easier cloning. Great work with @jennynathans.bsky.social, @troymcdiarmid.bsky.social and @jshendure.bsky.social . Happy recording!!

Mammalian genome writing: Unlocking new length scales for genome engineering The ability to design and engineer mammalian genomes across arbitrary length scales would transform biology and medicine. Such capabilities would enab…

Happy to share that our review on mammalian genome writing with Jack Atwater, Ran Brosh, Jef Boeke, @jshendure.bsky.social and Matt Maurano is now out in @cellpress.bsky.social!

www.sciencedirect.com/science/arti...

Summer Undergraduate Research Experience | HHMI The Cech Fellows Program is a paid, nine-week summer research experience empowering the next generation of scientific leaders.

Calling all rising juniors & seniors: Interested in biological or biomedical research? Applications for our ’26 Summer Undergraduate Research Experience Program are now open! Nine weeks, hands-on research, & mentorship from some of the nation’s top scientists — learn more: bit.ly/CechFellows

Happy Birthday to the Seattle Hub for Synthetic Biology! 🎂🎉

OTD with @chanzuckerberg.bsky.social and @uwmedicine.bsky.social, we launched #SeaSynBio with the goal to build tech that allows cells to record their own histories.

🔗 https://alleninstitute.org/division/seattle-hub-for-synthetic-biology

Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs Low-affinity transcription factor (TF) motifs are an important element of the cis-regulatory code, yet they are notoriously difficult to map and mechanistically incompletely understood, limiting our a...

We are pleased to announce a new preprint by @mlweilert.bsky.social: “Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs” (www.biorxiv.org/content/10.1...). See summary and longer recap below:

(TLDR; low-affinity motifs matter as pioneers!)

Our work developing a parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording is now out @natbiotech.nature.com

A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - Nature Biotechnology Prime editing in mammalian cells benefits from a comprehensive list of genetic parts.

A parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - @jshendure.bsky.social @troymcdiarmid.bsky.social @uwgenome.bsky.social go.nature.com/49eTPCu

🚀 Very excited to share the first major work from my PhD!!

We combined MPRA and CRISPRa in excitatory neurons to test and validate cis-regulation therapies for hundreds of haploinsufficient neurodevelopmental disorder genes. 🧬🔬

www.biorxiv.org/content/10.1...

Stoked to share our latest work entitled: “Large-scale discovery of neural enhancers for cis-regulation therapies”

shorturl.at/H3Qww

This is an enormous team effort that I had the honour of spearheading with Nick Page and Florence Chardon.

Bluetorial below.

Thrilled to share I’ve started my lab at Dartmouth’s Geisel School of Medicine! We focus on mapping cellular trajectories & TF networks in development and Mendelian disorders, exploring new therapies. Join us—postdocs, grads, and scientists welcome! sites.dartmouth.edu/qiulab/

Hierarchical lineage architecture of human and avian spinal cord revealed by single-cell genomic barcoding The formation of neural circuits depends on the precise spatial and temporal organisation of neuronal populations during development. In the vertebrate spinal cord, progenitors are patterned into mole...

Thrilled to share my main postdoc work with @jamesbriscoe.bsky.social

We used genomic barcoding + scRNAseq in chick & human embryos to reveal a lineage architecture that reshapes how we understand neural tube development & cell fate decisions
🧵👇

www.biorxiv.org/content/10.1...

This is one of the coolest figures I've seen in a while

Super excited about first Shendure/Baker Lab collaboration & preprint on a multiplex sequencing-based strategy for screening de novo proteome editors in mammalian cells. Kudos to the brilliant Chase Suiter (not here) & @greenahn.bsky.social on the work! Preprint here:
www.biorxiv.org/content/10.1...

There is also no space bar 😢

Developmental Biology and Disability.

“Developmental biology is fundamentally beautiful. We are no less beautiful for our variation. Instead, perhaps we are more so. Perhaps we are remarkable. Perhaps we are full of wonder.”

Insightful post by Bethan ⬇️👀
thenode.biologists.com/developmenta...

ATP-dependent remodeling of chromatin condensates reveals distinct mesoscale outcomes Adenosine triphosphate (ATP)–dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. We investigate effects of two major remod...

awesome new work by my @gladstoneinst.bsky.social and @ucsanfrancisco.bsky.social colleagues incl @vram142.bsky.social on how chromatin remodelers affect mesoscale chromatin organization www.science.org/doi/10.1126/...

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!

Saturation genome editing of BRCA1 across cell types accurately resolves cancer risk Germline pathogenic BRCA1 variants predispose women to breast and ovarian cancer. Despite accumulation of functional evidence for variants in BRCA1 , over half of reported single-nucleotide variants (...

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 The constraints that govern the evolution of gene expression patterns across development remain unclear. Single-cell RNA sequencing can detail these constraints by systematically profiling homologous ...

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!

Barcoded monoclonal embryoids are a potential solution to confounding bottlenecks in mosaic organoid screens Genetic screens in organoids hold tremendous promise for accelerating discoveries at the intersection of genomics and developmental biology. Embryoid bodies (EBs) are self-organizing multicellular str...

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...

Lineage recording in monoclonal gastruloids reveals heritable modes of early development Mammalian stem cells possess a remarkable capacity for self-organization, a property that underlies increasingly sophisticated in vitro models of early development. However, even under carefully contr...

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)

A multi-kingdom genetic barcoding system for precise clone isolation - Nature Biotechnology A barcoded CRISPR base editing system isolates target clones from complex mammalian, yeast and bacterial populations.

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 decodes Alu retrotransposition activity - Nature Communications Here, the authors develop a high-throughput assay to measure the jumping potential of thousands of transposons in parallel.

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...

SEARLE SCHOLARS PROGRAM NAMES 15 SCIENTISTS AS SEARLE SCHOLARS FOR 2025 Members of the new class of Searle Scholars pursue ground-breaking research in chemistry and the biomedical sciences. Each receives an award of $300,000 in flexible funding to support his, her, or …

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...