In vivo multimodal lineage tracing of mammalian development by DeepTrack barcoding
Year: 2026
Type: preprint
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.
Institutions: Fudan University, Westlake University, Second Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, German Cancer Research Center, Heidelberg University, Affiliated Hangzhou First People's Hospital, Westlake University, School of Medicine, Guangzhou Institutes of Biomedicine and Health, University of Hong Kong
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G3551078424, G7820722272
OpenAlex ID: W7204752491