A single cell transcriptional roadmap for cardiopharyngeal fate diversification

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...

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Bibliographic Details
Published inbioRxiv
Main Authors Wang, Wei, Niu, Xiang, Stuart, Tim, Jullian, Estelle, Mauck, William, Kelly, Robert G, Satija, Rahul, Christiaen, Lionel
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 19.02.2019
Subjects
Cardiac conditioning
Cardiomyocytes
Ciona
Data processing
Embryos
Gene expression
Genomics
Heart
MAP kinase
Mesoderm
Muscles
Pharynx
Ribonucleic acid
RNA
Tbx1 protein
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Summary: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. Footnotes * New data and analyses include single cell RNA-seq profiling of juvenile heart, and systematic comparison of single cell RNA-seq from Ciona and mouse embryos, identifying shared cardiopharyngeal markers. * https://christiaenlab.shinyapps.io/tvc-lineage/
DOI:10.1101/150235