Single-cell lineage tracing of human neuromesoderm organoids reveals TBX6-mediated posterior mesoderm fate diversification

Brachyury expression levels predict lineage potential and axis-forming ability of in vitro-derived neuromesodermal progenitors

Neuromesodermal progenitors (NMPs) produce the spinal cord and musculoskeleton in the elongating anterior-posterior axis. In vivo, NMPs possess dual potency, coinciding with regions coexpressing SOX2 and Brachyury (TBXT). In vitro, SOX2/TBXT co-expressing cells can be produced from pluripotent cells and, like their in...

Engineered dual-gastruloid model for foregut-pharyngeal mesoderm co-development

Hox/Meis-dependent gene-regulatory transition underlies cardiopharyngeal neural crest diversification

Neural crest cells (NCCs) are multipotent migratory cells essential for cardiac development, yet the lineage trajectories and gene regulatory networks underlying their differentiation in the cardiopharyngeal region remain unclear. Here, we integrate single-cell RNA-seq, spatial transcriptomics, and multiomic analyses t...

Transcriptomic Analysis Identifies Transient Mesendodermal State and Lineage Divergence in Human Pluripotent Stem Cell Differentiation

Human pluripotent stem cells serve as a vital model for studying early human lineage specification, yet conventional assessments relying on endpoint canonical markers of the three germ layers may overlook transient intermediate states and broader cellular programs. Here we combined directed differentiation of human ind...

In utero barcoding of mouse mesoderm reveals the clonal architecture of organ mesenchyme

The mesoderm coordinates organogenesis and generates the cardiovascular, visceral and musculoskeletal systems, yet in mammals this germ layer is difficult to access, impeding its genetic manipulation and study. Here, we establish embryonic day (E) 7.5 exocoelomic cavity nano-injection as a scalable route for selective...

In vivo multimodal lineage tracing of mammalian development by DeepTrack barcoding

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 fat...