title: Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.
abstract: In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kokkinopoulos
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Rie
authors.initials: R
authors.lastname: Saba
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Physiology and Pathology, University of São Paulo State - UNESP, Araraquara School of Dentistry, Araraquara, São Paulo, Brazil.
authors.forename: Prashant
authors.initials: P
authors.lastname: Ruchaya
authors.affiliation: Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cabrera
authors.affiliation: Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Monika
authors.initials: M
authors.lastname: Struebig
authors.affiliation: Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Barnes
authors.affiliation: Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Terry
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Shintani
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Coppen
authors.affiliation: Department of Developmental Genetics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Shiratori
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Torath
authors.initials: T
authors.lastname: Ameen
authors.affiliation: Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Mein
authors.affiliation: Department of Developmental Genetics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Ken
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Kenta
authors.initials: K
authors.lastname: Yashiro
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D011247:Pregnancy; D059010:Single-Cell Analysis / Q000379:methods*; D059467:Transcriptome