Embryonic origins of adult pluripotent stem cells

Although adult pluripotent stem cells (aPSCs) are found in many animal lineages, mechanisms for their for-mation during embryogenesis are unknown. Here, we leveraged Hofstenia miamia, a regenerative worm that possesses collectively pluripotent aPSCs called neoblasts and produces manipulable embryos. Lineage tracing and functional experiments revealed that one pair of blastomeres gives rise to cells that resemble neoblasts in distribution, behavior, and gene expression. In Hofstenia, aPSCs include transcriptionally distinct subpopulations that express markers associated with differentiated tissues; our data suggest that despite their heterogeneity, aPSCs are derived from one lineage, not from multiple tissue-specific lineages during development. Next, we combined single-cell transcriptome profiling across development with neo-blast cell-lineage tracing and identified a molecular trajectory for neoblast formation that includes transcrip-tion factors Hes, FoxO, and Tbx. This identification of a cellular mechanism and molecular trajectory for aPSC formation opens the door for in vivo studies of aPSC regulation and evolution.

Automated summary

This study reveals the cellular mechanism and molecular trajectory for the formation of adult pluripotent stem cells (aPSCs) during embryonic development. By utilizing lineage tracing and single-cell transcriptome profiling, the researchers identified a molecular trajectory for neoblast formation and showed that aPSCs derive from one lineage instead of multiple tissue-specific lineages.