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PreprintCC BY-NCbioRxiv

In vivo multimodal lineage tracing of mammalian development by DeepTrack barcoding

  • C. Guo
  • J. Jiang
  • X. Wang
  • X. Huang
  • S. Zhang
  • C. Shao
  • M. Zhang
  • X. Hu
  • W. Yang
  • F. Shang
  • X. Wang
  • H. Zhai
9 more authors
  • Q. Du
  • F. Liu
  • D. He
  • X. Liu
  • G. Peng
  • S. Cheng
  • Y. Zhang
  • D. Pei1
  • W. Pei1
  1. 1Westlake University
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Abstract

A comprehensive recording of cell fate transitions and underlying molecular changes remains a fundamental goal in developmental biology. Here, we present DeepTrack, a lineage tracing mouse model that integrates in situ cellular barcoding with high-throughput, single-cell multi-omics to simultaneously profile clonal fates, transcriptomic states, and chromatin accessibility. Using DeepTrack, we profiled clonal behaviors during gastrulation and early organogenesis, uncovered early fate priming within epiblast clones, and revealed clonal architecture within distinct regions of the nervous system. Embryo-wide multi-omic lineage tracing at single-cell resolution revealed transcriptional and epigenetic programs underlying fate commitment in neuromesodermal progenitors (NMPs). Clonal tracing with multi-omic profiles enabled inference of fate-associated gene-regulatory networks and identified the transcription factor Cdx2 as a key regulator of mesodermal specification in NMPs. Genetic perturbation of Cdx2 in chimeric embryos impaired paraxial mesoderm differentiation. Together, DeepTrack provides a versatile framework for decoding multimodal regulation of cell fate across diverse developmental contexts.

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Cite

BibTeXRIS
BibTeX
@misc{guo2026vivo,
  title = {{In vivo multimodal lineage tracing of mammalian development by DeepTrack barcoding}},
  author = {C. Guo and J. Jiang and X. Wang and X. Huang and S. Zhang and C. Shao and M. Zhang and X. Hu and W. Yang and F. Shang and X. Wang and H. Zhai and Q. Du and F. Liu and D. He and X. Liu and G. Peng and S. Cheng and Y. Zhang and D. Pei and W. Pei},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.29.748052},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.29.748052v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - In vivo multimodal lineage tracing of mammalian development by DeepTrack barcoding
AU  - C. Guo
AU  - J. Jiang
AU  - X. Wang
AU  - X. Huang
AU  - S. Zhang
AU  - C. Shao
AU  - M. Zhang
AU  - X. Hu
AU  - W. Yang
AU  - F. Shang
AU  - X. Wang
AU  - H. Zhai
AU  - Q. Du
AU  - F. Liu
AU  - D. He
AU  - X. Liu
AU  - G. Peng
AU  - S. Cheng
AU  - Y. Zhang
AU  - D. Pei
AU  - W. Pei
PY  - 2026
DA  - 2026/08/29
PB  - bioRxiv
DO  - 10.64898/2026.08.29.748052
UR  - https://www.biorxiv.org/content/10.64898/2026.08.29.748052v1
AB  - A comprehensive recording of cell fate transitions and underlying molecular changes remains a fundamental goal in developmental biology. Here, we present DeepTrack, a lineage tracing mouse model that integrates in situ cellular barcoding with high-throughput, single-cell multi-omics to simultaneously profile clonal fates, transcriptomic states, and chromatin accessibility. Using DeepTrack, we profiled clonal behaviors during gastrulation and early organogenesis, uncovered early fate priming within epiblast clones, and revealed clonal architecture within distinct regions of the nervous system. Embryo-wide multi-omic lineage tracing at single-cell resolution revealed transcriptional and epigenetic programs underlying fate commitment in neuromesodermal progenitors (NMPs). Clonal tracing with multi-omic profiles enabled inference of fate-associated gene-regulatory networks and identified the transcription factor Cdx2 as a key regulator of mesodermal specification in NMPs. Genetic perturbation of Cdx2 in chimeric embryos impaired paraxial mesoderm differentiation. Together, DeepTrack provides a versatile framework for decoding multimodal regulation of cell fate across diverse developmental contexts.
ER  -