title: CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells.
abstract: The generation of tissue-specific cell types from human embryonic stem cells (hESCs) is critical for the development of future stem cell-based regenerative therapies. Here, we identify CD13 and ROR2 as cell-surface markers capable of selecting early cardiac mesoderm emerging during hESC differentiation. We demonstrate that the CD13+/ROR2+ population encompasses pre-cardiac mesoderm, which efficiently differentiates to all major cardiovascular lineages. We determined the engraftment potential of CD13+/ROR2+ in small (murine) and large (porcine) animal models, and demonstrated that CD13+/ROR2+ progenitors have the capacity to differentiate toward cardiomyocytes, fibroblasts, smooth muscle, and endothelial cells in vivo. Collectively, our data show that CD13 and ROR2 identify a cardiac lineage precursor pool that is capable of successful engraftment into the porcine heart. These markers represent valuable tools for further dissection of early human cardiac differentiation, and will enable a detailed assessment of human pluripotent stem cell-derived cardiac lineage cells for potential clinical applications.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine at UCLA, 675 Charles E Young Drive South, Room 3645, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA; Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
authors.forename: Rhys J P
authors.initials: RJ
authors.lastname: Skelton
authors.affiliation: Bio-X Program, Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Bevin
authors.initials: B
authors.lastname: Brady
authors.affiliation: Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine at UCLA, 675 Charles E Young Drive South, Room 3645, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA.
authors.forename: Suhail
authors.initials: S
authors.lastname: Khoja
authors.affiliation: Bio-X Program, Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Debashis
authors.initials: D
authors.lastname: Sahoo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine at UCLA, 675 Charles E Young Drive South, Room 3645, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA.
authors.forename: James
authors.initials: J
authors.lastname: Engel
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
authors.forename: Deevina
authors.initials: D
authors.lastname: Arasaratnam
authors.affiliation: Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine at UCLA, 675 Charles E Young Drive South, Room 3645, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA.
authors.forename: Kholoud K
authors.initials: KK
authors.lastname: Saleh
authors.affiliation: Bio-X Program, Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Oscar J
authors.initials: OJ
authors.lastname: Abilez
authors.affiliation: Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine at UCLA, 675 Charles E Young Drive South, Room 3645, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
authors.forename: Edouard G
authors.initials: EG
authors.lastname: Stanley
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Elefanty
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Murray
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Elliott
authors.affiliation: Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine at UCLA, 675 Charles E Young Drive South, Room 3645, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA. Electronic address: rardehali@mednet.ucla.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Ardehali
mesh_terms: D000818:Animals; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling / Q000379:methods; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D018826:CD13 Antigens