Lineage tracing reveals asynchronous fate restriction in mouse embryos and stem cell-derived embryo models

  1. Yunzheng Liu
  2. Jihye Park
  3. Laura Amaya
  4. Sergi Junyent
  5. Xiangkai Sun
  6. Jiabao Sean Xiao
  7. Yuqi Wang
  8. Hao Wang
  9. Yunrui Lu
  10. Shoma Nakagawa
  11. Sung-Eun Park
  12. Wenqi Hu
  13. Shichen Liu
  14. Jiangbo Wei
  15. Hyongbum Henry Kim
  16. Matthew Thomson
  17. Cheng-Wei Ju
  18. Marianne E. Bronner
  19. Junhong Choi
  20. Magdalena Zernicka-Goetz
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Abstract

How a flexible mammalian embryo gives rise to a reproducible body plan remains unclear, partly because cell lineages cannot be followed continuously in vivo. We combined DNA Typewriter lineage recording with tetraploid complementation to reconstruct high-resolution single-cell genealogies across mouse development and built FateVec, an analysis framework that infers fate-bias dynamics and lineage-associated transcriptional programs from reconstructed phylogenies. Loss of developmental potential proved progressive and asynchronous, with multiple lineages acquiring detectable fate bias before morphological diversification at gastrulation. Within the neural crest, most cells remained multipotent over an extended window, while independent founder clades differed markedly in restriction timing. Extending lineage recording to a stem-cell-derived embryo model revealed that cells with shared transcriptional identities can arise from distinct lineage relationships. We further found embryonic-lineage contributions to extraembryonic-like states, exposing an unexplored lineage plasticity. This lineage-resolved view of embryogenesis reveals that cell identity alone predicts neither developmental ancestry nor the timing of fate restriction.

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  1. Version published to 10.64898/2026.10.06.756974v2 on bioRxiv
  2. Mentioned by @choijunhong.bsky.social on Bluesky

    New preprint with Zernicka-Goetz lab (@zernickagoetz.bsky.social) on lineage reconstruction in mouse embryos and stem cell-derived embryo models, led by Yunzheng Liu! (1/13) www.biorxiv.org/content/10.6...

  3. Mentioned by @rridrobot.bsky.social on Bluesky

    Authors used B6D2F1 in their study. Including #RRIDs will make this less ambiguous. SciScore made a table with this resource, see “Automated Services” module (download as csv, xml or #jats) #STMpublishing #RRID

  4. Mentioned by @prepub-singlecell.bsky.social on Bluesky

    Lineage tracing reveals asynchronous fate restriction in mouse embryos and stem cell-derived embryo models #SingleCell 🧪🧬🖥️ https://www.biorxiv.org/content/10.64898/2026.10.06.756974v1

  5. Mentioned by @biorxiv-devbio.bsky.social on Bluesky

    Lineage tracing reveals asynchronous fate restriction in mouse embryos and stem cell-derived embryo models https://www.biorxiv.org/content/10.64898/2026.10.06.756974v1

  6. Mentioned by @biorxivpreprint.bsky.social on Bluesky

    Lineage tracing reveals asynchronous fate restriction in mouse embryos and stem cell-derived embryo models https://www.biorxiv.org/content/10.64898/2026.10.06.756974v1

  7. Version published to 10.64898/2026.10.06.756974v1 on bioRxiv