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A single cell transcriptional roadmap for cardiopharyngeal fate diversification

By Wei Wang, Xiang Niu, Tim Stuart, Estelle Jullian, William Mauck, Robert G. Kelly, Rahul Satija, Lionel Christiaen

Posted 15 Jun 2017
bioRxiv DOI: 10.1101/150235 (published DOI: 10.1038/s41556-019-0336-z)

In vertebrates, multipotent progenitors located in the pharyngeal mesoderm form cardiomyocytes and branchiomeric head muscles, but the dynamic gene expression programs and mechanisms underlying cardiopharyngeal multipotency and heart vs. head muscle fate choices remain elusive. Here, we used single cell genomics in the simple chordate model Ciona, to reconstruct developmental trajectories forming first and second heart lineages, and pharyngeal muscle precursors, and characterize the molecular underpinnings of cardiopharyngeal fate choices. We show that FGF-MAPK signaling maintains multipotency and promotes the pharyngeal muscle fate, whereas signal termination permits the deployment of a pan-cardiac program, shared by the first and second lineages, to define heart identity. In the second heart lineage, a Tbx1/10-Dach pathway actively suppresses the first heart lineage program, conditioning later cell diversity in the beating heart. Finally, cross-species comparisons between Ciona and the mouse evoke the deep evolutionary origins of cardiopharyngeal networks in chordates.

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