title: Development of Bipotent Cardiac/Skeletal Myogenic Progenitors from MESP1+ Mesoderm.
abstract: The branchiomeric skeletal muscles co-evolved with new chambers of the heart to enable predatory feeding in chordates. These co-evolved tissues develop from a common population in anterior splanchnic mesoderm, referred to as cardiopharyngeal mesoderm (CPM). The regulation and development of CPM are poorly understood. We describe an embryonic stem cell-based system in which MESP1 drives a PDGFRA+ population with dual cardiac and skeletal muscle differentiation potential, and gene expression resembling CPM. Using this system, we investigate the regulation of these bipotent progenitors, and find that cardiac specification is governed by an antagonistic TGFβ-BMP axis, while skeletal muscle specification is enhanced by Rho kinase inhibition. We define transcriptional signatures of the first committed CPM-derived cardiac and skeletal myogenic progenitors, and discover surface markers to distinguish cardiac (PODXL+) from the skeletal muscle (CDH4+) CPM derivatives. These tools open an accessible window on this developmentally and evolutionarily important population.
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Sunny Sun-Kin
authors.initials: SS
authors.lastname: Chan
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Hagen
authors.affiliation: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Swanson
authors.affiliation: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Karly A
authors.initials: KA
authors.lastname: Boll
authors.affiliation: Stem Cells Department, R&D Systems, Inc., Minneapolis, MN 55413, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Aho
authors.affiliation: Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Thomson
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota, Cancer and Cardiovascular Research Building 4-127, 2231 6th Street Southeast, Minneapolis, MN 55455, USA. Electronic address: kyba@umn.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyba
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D012795:Sialoglycoproteins; C101538:Mesp1 protein, mouse; C083970:R-cadherin; C001643:podocalyxin
keywords: Mesp1; cardiac development; cardiopharyngeal mesoderm; mesoderm; skeletal myogenesis