CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells

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 differentiat...

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Main Authors: Rhys J.P. Skelton, Bevin Brady, Suhail Khoja, Debashis Sahoo, James Engel, Deevina Arasaratnam, Kholoud K. Saleh, Oscar J. Abilez, Peng Zhao, Edouard G. Stanley, Andrew G. Elefanty, Murray Kwon, David A. Elliott, Reza Ardehali
Format: Article
Language:English
Published: Elsevier 2016-01-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671115003422
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author Rhys J.P. Skelton
Bevin Brady
Suhail Khoja
Debashis Sahoo
James Engel
Deevina Arasaratnam
Kholoud K. Saleh
Oscar J. Abilez
Peng Zhao
Edouard G. Stanley
Andrew G. Elefanty
Murray Kwon
David A. Elliott
Reza Ardehali
author_facet Rhys J.P. Skelton
Bevin Brady
Suhail Khoja
Debashis Sahoo
James Engel
Deevina Arasaratnam
Kholoud K. Saleh
Oscar J. Abilez
Peng Zhao
Edouard G. Stanley
Andrew G. Elefanty
Murray Kwon
David A. Elliott
Reza Ardehali
author_sort Rhys J.P. Skelton
collection DOAJ
description 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.
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spelling doaj.art-2d1db96c76b8472f8dd7cec5338423d62022-12-22T00:56:20ZengElsevierStem Cell Reports2213-67112016-01-01619510810.1016/j.stemcr.2015.11.006CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem CellsRhys J.P. Skelton0Bevin Brady1Suhail Khoja2Debashis Sahoo3James Engel4Deevina Arasaratnam5Kholoud K. Saleh6Oscar J. Abilez7Peng Zhao8Edouard G. Stanley9Andrew G. Elefanty10Murray Kwon11David A. Elliott12Reza Ardehali13Division 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, USABio-X Program, Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USADivision 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, USABio-X Program, Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USADivision 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, USAMurdoch Children’s Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, AustraliaDivision 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, USABio-X Program, Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USADivision 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, USAMurdoch Children’s Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, AustraliaMurdoch Children’s Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, AustraliaDivision of Cardiothoracic Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USAMurdoch Children’s Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, AustraliaDivision 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, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2213671115003422
spellingShingle Rhys J.P. Skelton
Bevin Brady
Suhail Khoja
Debashis Sahoo
James Engel
Deevina Arasaratnam
Kholoud K. Saleh
Oscar J. Abilez
Peng Zhao
Edouard G. Stanley
Andrew G. Elefanty
Murray Kwon
David A. Elliott
Reza Ardehali
CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells
Stem Cell Reports
title CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells
title_full CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells
title_fullStr CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells
title_full_unstemmed CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells
title_short CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells
title_sort cd13 and ror2 permit isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells
url http://www.sciencedirect.com/science/article/pii/S2213671115003422
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