A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis
- 1Department of Genome Sciences, University of Washington, Seattle, WA, USA
Abstract
Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibrated, parsimony-supported, zygote-rooted phylogeny of 1.28M transcriptionally-profiled cells. A burst of editing unequivocally marks the daughters of the first cleavage, which serve as inline replicates. We quantify clonal dominance arising during gastrulation. Tree siblings share cell type far above chance; heterotypic siblings mark terminal differentiations. Temporal sweeps of clade co-occurrence recover a dated hierarchy of cell-type couplings; imputed labels for internal nodes recapitulate known state paths. A lineage-anchored ontogeny of mammalian development, long out of reach, is coming into view.
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BibTeX
@misc{yu2026typewriter,
title = {{A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis}},
author = {Q. Yu and H. Kim and S. Seidel and J. F. Acosta-Clark and B. K. Martin and K. O'Connor and R. M. Daza and M. Gasperini and J. F. Nathans and M. Lam and E. Gamo and S. Vijay Kumar and L. Kuo and J.-B. Lalanne and K. Simeonov and M. Pepper and C. Trapnell and J. M. Gray and J. Choi and C. Qiu and J. Shendure},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.29.741625},
url = {https://www.biorxiv.org/content/10.64898/2026.07.29.741625v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis
AU - Q. Yu
AU - H. Kim
AU - S. Seidel
AU - J. F. Acosta-Clark
AU - B. K. Martin
AU - K. O'Connor
AU - R. M. Daza
AU - M. Gasperini
AU - J. F. Nathans
AU - M. Lam
AU - E. Gamo
AU - S. Vijay Kumar
AU - L. Kuo
AU - J.-B. Lalanne
AU - K. Simeonov
AU - M. Pepper
AU - C. Trapnell
AU - J. M. Gray
AU - J. Choi
AU - C. Qiu
AU - J. Shendure
PY - 2026
DA - 2026/07/29
PB - bioRxiv
DO - 10.64898/2026.07.29.741625
UR - https://www.biorxiv.org/content/10.64898/2026.07.29.741625v2
AB - Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibrated, parsimony-supported, zygote-rooted phylogeny of 1.28M transcriptionally-profiled cells. A burst of editing unequivocally marks the daughters of the first cleavage, which serve as inline replicates. We quantify clonal dominance arising during gastrulation. Tree siblings share cell type far above chance; heterotypic siblings mark terminal differentiations. Temporal sweeps of clade co-occurrence recover a dated hierarchy of cell-type couplings; imputed labels for internal nodes recapitulate known state paths. A lineage-anchored ontogeny of mammalian development, long out of reach, is coming into view.
ER -