A single-cell transcriptional roadmap for cardiopharyngeal fate diversification

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

Research output: Contribution to journalArticle

Abstract

In vertebrates, multipotent progenitors located in the pharyngeal mesoderm form cardiomyocytes and branchiomeric head muscles, but the dynamic gene expression programmes and mechanisms underlying cardiopharyngeal multipotency and heart versus 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 signalling maintains multipotency and promotes the pharyngeal muscle fate, whereas signal termination permits the deployment of a pan-cardiac programme, shared by the first and second heart lineages, to define heart identity. In the second heart lineage, a Tbx1/10-Dach pathway actively suppresses the first heart lineage programme, 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.

Original languageEnglish (US)
Pages (from-to)674-686
Number of pages13
JournalNature Cell Biology
Volume21
Issue number6
DOIs
StatePublished - Jun 1 2019

ASJC Scopus subject areas

  • Cell Biology

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