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Reposted by Jonathan Weissman Lab

Mann Lab @mannlab.bsky.social · 28/05/2026

1/5 Cell identity is written in the proteome, not in the DNA, and not always in the RNA. Out on bioRxiv today: The first cell type-resolved, MS-based proteomic atlas of the human body. www.biorxiv.org/content/10.6...

biorxiv.org

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Reposted by Jonathan Weissman Lab

Dr M @ivalaine.bsky.social · 28/05/2026

Are you saying their are proteins being made not transcribed from any RNA? And there is RNA not encoded by DNA?

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

This has been a wonderful collaboration between our group and Zachary Smith’s Group @yalemedicine.bsky.social and @molgen.mpg.de with important contributions from Nir Yosef @weizenbauminstitut.bsky.social, @zhuanglab.bsky.social @harvard.edu, and Kyle Loh @stanfordpress.bsky.social

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

There is a ton more in the paper and we would look forward to everyone’s feedback! Stay tuned for exciting next steps!

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

The scale and density of this dataset provide a framework for quantifying cell fate restriction dynamics–the frequency, reproducibility, and variance of fate decisions across embryos–and enabling a unified view of embryogenesis to uncover core principles of mouse development

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

Fourth: Transcriptional boundaries ≠ lineage boundaries. At the midbrain-hindbrain boundary, clades often span both regions despite distinct transcriptional identities. Regional identities emerge from later specification events, not early lineage compartmentalization

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

Our trees confirm they arise from lateral plate, intermediate, AND paraxial mesoderm, yet retain clear transcriptional memories of where they came from

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

Third: Cell types can converge on shared transcriptional programs from distinct lineage origins. Endothelial cells are a classic example. Whether they arise from paraxial mesoderm has been debated for decades

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

Second: Germ layer fate restriction begins before gastrulation and extends beyond it. Detectable germ layer bias in the epiblast first appears ~E4. By contrast, in the growing tailbud bipotent axial progenitors continue to specify additional mesoderm and ectoderm through E9.5

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

First: Despite the non-deterministic nature of mammalian development, lineage architecture is highly reproducible across embryos. Progenitor numbers, clonal outputs, and the timing of shared ancestry between cell type pairs all show minimal variation between replicates

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

What did we find? We dissected fate restriction across the developing notochord, heart, neural crest, and tailbud. From these case studies, a few high-level principles about mammalian development emerged

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

We engineered mESCs with the PEtracer system, which continuously installs heritable marks at >100 editable sites throughout development. Using these cells, we generated high-grade chimeric embryos (up to 99%) and reconstructed lineage trees resolving ~75% of cell divisions

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

A complete cell fate map–the record of every progenitor-progeny relationship–would transform how we understand development. But the scale, cellular diversity, and in utero nature of mammalian embryogenesis have kept an embryo-wide quantitative view out of reach

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

Using PEtracer (www.science.org/doi/10.1126/...) we reconstructed lineage trees for 16 mouse embryos sampled at half-day intervals from E7.5 to E10.0. We profiled ~50% of cells from each embryo with scRNA-seq, capturing late and rare fate restriction events that would be missed with subsampling

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Jonathan Weissman Lab @weissmanlab.bsky.social · 09/05/2026

Excited to share a new preprint from the lab led by @lukekoblan.bsky.social and William Colgan in which we describe our efforts to define a quantitative cell fate map of mouse embryogenesis! www.biorxiv.org/content/10.6...

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Jonathan Weissman Lab @weissmanlab.bsky.social · 01/12/2024

Congratulations to James Numez and collaborators for their RENDER platform for delivering epigenetic editors using engineered VLPs. RENDER broadly advances our ability to with critical fundamental and therapeutic applications. biorxiv.org/content/10.1...

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Jonathan Weissman Lab @weissmanlab.bsky.social · 22/11/2024

One key component of Perturb-Multi is in vivo Perturb-seq of formaldehyde-fixed tissue, enabled by the Flex reagents from @10xGenomics.

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Jonathan Weissman Lab @weissmanlab.bsky.social · 22/11/2024

Perturb-Multi generates rich, multimodal data that can generate fundamentally new insights about the impact of genetic perturbations on tissue function. Check it out!

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Jonathan Weissman Lab @weissmanlab.bsky.social · 22/11/2024

We used lentiviral delivery of sgRNAs to create genetic mosaic organs, separately knocking out hundreds of genes in the liver of a single mouse.

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Jonathan Weissman Lab @weissmanlab.bsky.social · 22/11/2024

Perturb-Multi is a platform for pooled genetic screens in intact mammalian tissue with spatial (MERFISH and multiplexed immunofluorescence) and scRNA-seq-based phenotyping.

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