In vivo multimodal lineage tracing of mammalian development by DeepTrack barcoding

In a groundbreaking development for developmental biology, researchers have unveiled DeepTrack, an innovative lineage tracing mouse model. This model combines in situ cellular barcoding with high-throughput, single-cell multi-omics, enabling simultaneous profiling of clonal fates, transcriptomic states, and chromatin accessibility.

Utilizing DeepTrack, scientists were able to meticulously study clonal behaviors during gastrulation and early organogenesis, uncovering early fate priming within epiblast clones and revealing clonal architecture within various regions of the nervous system.

The model offers an unprecedented level of resolution, capturing embryo-wide multi-omic lineage tracing at the single-cell level. This approach provided a comprehensive view of the transcriptional and epigenetic programs that underlie fate commitment in neuromesodermal progenitors (NMPs). Through clonal tracing and multi-omic profiles, researchers were able to infer fate-associated gene-regulatory networks and identify transcription factor Cdx2 as a critical regulator of mesodermal specification within NMPs.

Further investigation into the genetic perturbation of Cdx2 in chimeric embryos revealed significant implications for paraxial mesoderm differentiation. By providing a versatile framework for decoding multimodal regulation of cell fate, DeepTrack offers a powerful tool for unraveling the complex regulatory mechanisms underlying diverse developmental contexts.