1/13
The human body runs on one genome—but every cell reads it differently. How?
To find out, we need to know both gene expression and chromatin accessibility in the same nucleus.
So we did, across 21 adult tissues and nearly half a million nuclei. 🧵
🔗 https://t.co/qwMv6oaprM
Thrilled to post thread re: new single-cell lineage of mouse embryo reconstructed w/ DNA Typewriter. One animal, zygote to late organogenesis (E13.5). Tree has 1,340,794 transcriptionally profiled, annotated tips (cells), 1,142,588 dated internal nodes, rooted at zygote
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1/13
The human body runs on one genome—but every cell reads it differently. How?
To find out, we need to know both gene expression and chromatin accessibility in the same nucleus.
So we did, across 21 adult tissues and nearly half a million nuclei. 🧵
🔗 https://t.co/qwMv6oaprM
@HooReallyCares Yes. Figure 3g shows a few examples of locked regions that overlap oncogenes. However, a more comprehensive analysis is needed, and there remains considerable room for further exploration.
6/13
We mapped 871,177 cell-type-specific regulatory element–gene associations.
Genomic proximity was not always enough: 36% of distal associations involved a non-nearest gene.
@vagaryplay Thank you! We’re currently uploading the data to the CELLxGENE and GTEx portals. We’ll share the resource as soon as it’s publicly available!
13/13
We are deeply grateful to the GTEx/ENTEx donors and their families.
Many thanks to @JD_Buenrostro, @KArdlie, and all my colleagues for their support along the way!
10/13
We next modeled the effects of 548,656 fine-mapped trait- and disease-associated variants across 35 primary cell types.
We identified 18,133 variants with large predicted accessibility effects. Most were cell-type restricted; 1,120 had broadly distributed effects.
12/13
Cellular context matters: the same gene or variant can behave differently in different cells.
This atlas helps prioritize which regulatory element may influence which gene—and in which cell.
More detail in
🔗 https://t.co/qwMv6o9RCe
5/13
Regulatory activity reflected both cell identity and tissue context.
Shared cell types preserved a core regulatory program across organs, while a smaller set of elements adapted to the local tissue environment.
3/13
Integrating RNA and chromatin accessibility resolved:
• 9 cell lineages
• 61 broad cell types
• 313 finer transcriptional subclusters
This provided a common framework for comparing regulatory programs across the body.
4/13
We mapped 1,085,062 candidate regulatory elements across the genome, including 161,270 absent from the ENCODE registry.
Novel elements were enriched for transposable-element sequence, showed lower evolutionary conservation, and were more cell-type-specific.
2/13
We profiled 459,856 nuclei from 21 tissues and 4 adult donors, including 160,688 nuclei with paired RNA and chromatin-accessibility.
That pairing lets us relate accessible regulatory DNA to gene expression within matched nuclei.
Very happy to announce that I’ll be launching my lab at WashU in 2027! We’ll build on this work to uncover the mechanisms and diversity of epigenetic memory and its role in human disease.
Hiring at all levels to start early 2027 — learn more or reach out: https://t.co/ysnkFHVVAo