title: Foxa2 identifies a cardiac progenitor population with ventricular differentiation potential.
abstract: The recent identification of progenitor populations that contribute to the developing heart in a distinct spatial and temporal manner has fundamentally improved our understanding of cardiac development. However, the mechanisms that direct atrial versus ventricular specification remain largely unknown. Here we report the identification of a progenitor population that gives rise primarily to cardiovascular cells of the ventricles and only to few atrial cells (<5%) of the differentiated heart. These progenitors are specified during gastrulation, when they transiently express Foxa2, a gene not previously implicated in cardiac development. Importantly, Foxa2+ cells contribute to previously identified progenitor populations in a defined pattern and ratio. Lastly, we describe an analogous Foxa2+ population during differentiation of embryonic stem cells. Together, these findings provide insight into the developmental origin of ventricular and atrial cells, and may lead to the establishment of new strategies for generating chamber-specific cell types from pluripotent stem cells.
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, Box 1040, 1470 Madison Avenue, New York, New York 10029, USA.|Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Bardot
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, Box 1040, 1470 Madison Avenue, New York, New York 10029, USA.|Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Damelys
authors.initials: D
authors.lastname: Calderon
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, Box 1040, 1470 Madison Avenue, New York, New York 10029, USA.|Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Santoriello
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, Box 1040, 1470 Madison Avenue, New York, New York 10029, USA.|Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Songyan
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Kakit
authors.initials: K
authors.lastname: Cheung
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Bharati
authors.initials: B
authors.lastname: Jadhav
authors.affiliation: Institute of Diabetes and Regeneration Research at the Helmholtz Zentrum München, German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Burtscher
authors.affiliation: Departments of Cell and Developmental Biology and Medicine, Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Artap
authors.affiliation: Departments of Cell and Developmental Biology and Medicine, Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Rajan
authors.initials: R
authors.lastname: Jain
authors.affiliation: Departments of Cell and Developmental Biology and Medicine, Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Epstein
authors.affiliation: Institute of Diabetes and Regeneration Research at the Helmholtz Zentrum München, German Center for Diabetes Research (DZD), Neuherberg 85764, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, Box 1040, 1470 Madison Avenue, New York, New York 10029, USA.|Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Gouon-Evans
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sharp
authors.affiliation: Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, Box 1040, 1470 Madison Avenue, New York, New York 10029, USA.|Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Dubois
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D054262:Gastrulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000166:cytology / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology* / Q000000981:diagnostic imaging / Q000254:growth & development*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: C496503:Foxa2 protein, mouse; D051542:Hepatocyte Nuclear Factor 3-beta