A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis
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 1.28 million 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.
Authors
- Chengxiang Qiu (ORCID: https://orcid.org/0000-0002-6346-8669)
- Shruthi VijayKumar (ORCID: https://orcid.org/0000-0001-6679-1261)
- Beth Martin (ORCID: https://orcid.org/0000-0002-9661-014X)
- Jean‐Benoît Lalanne (ORCID: https://orcid.org/0000-0001-8753-0669)
- Cole Trapnell (ORCID: https://orcid.org/0000-0002-8105-4347)
- Riza M. Daza (ORCID: https://orcid.org/0000-0003-1635-8675)
- Marion Pepper (ORCID: https://orcid.org/0000-0001-7278-0147)
- Sophie Seidel (ORCID: https://orcid.org/0000-0002-4484-9888)
- Jenny F. Nathans (ORCID: https://orcid.org/0000-0002-0276-734X)
- Junhong Choi (ORCID: https://orcid.org/0000-0001-9291-5977)
- Molly J. Gasperini (ORCID: https://orcid.org/0000-0003-4559-8432)
- Kamen P. Simeonov (ORCID: https://orcid.org/0000-0003-2194-3668)
- Jay Shendure (ORCID: https://orcid.org/0000-0002-1516-1865)
- Lauren M. Kuo (ORCID: https://orcid.org/0009-0005-2153-5041)
- Haedong Kim (ORCID: https://orcid.org/0000-0003-3589-0042)
- James F. Clark (ORCID: https://orcid.org/0000-0002-8659-6348)
- Qi Yu (ORCID: https://orcid.org/0009-0007-7215-2133)
- Jesse M. Gray (ORCID: https://orcid.org/0000-0003-4560-8813)
- Kyle O'Connor
- Elena Gamo
- Maggie Lam
Institutions
- Dartmouth College (US)
- Howard Hughes Medical Institute (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Biodesigns (United States) (US)
- Brotman Baty Institute (US)
- Allen Institute (US)
Publication Details
- Journal
- Science
- Published
- 2026-10-08
- DOI
- https://doi.org/10.1126/science.ael0508
- Citations
- 1
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 1.94