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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2016-01-01
|
Series: | Stem Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115003422 |
_version_ | 1818532554390634496 |
---|---|
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. |
first_indexed | 2024-12-11T17:47:02Z |
format | Article |
id | doaj.art-2d1db96c76b8472f8dd7cec5338423d6 |
institution | Directory Open Access Journal |
issn | 2213-6711 |
language | English |
last_indexed | 2024-12-11T17:47:02Z |
publishDate | 2016-01-01 |
publisher | Elsevier |
record_format | Article |
series | Stem Cell Reports |
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 |
work_keys_str_mv | AT rhysjpskelton cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT bevinbrady cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT suhailkhoja cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT debashissahoo cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT jamesengel cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT deevinaarasaratnam cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT kholoudksaleh cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT oscarjabilez cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT pengzhao cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT edouardgstanley cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT andrewgelefanty cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT murraykwon cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT davidaelliott cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells AT rezaardehali cd13andror2permitisolationofhighlyenrichedcardiacmesodermfromdifferentiatinghumanembryonicstemcells |