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

Stem Cell Reports
Rhys J P SkeltonReza Ardehali

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.

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Citations

Sep 1, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Damelys CalderonNicole Dubois
Dec 8, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Philip TannenbergKarin Tran-Lundmark
Feb 23, 2018·Nature Communications·Konstantina-Ioanna SeretiReza Ardehali
Dec 11, 2019·Cold Spring Harbor Perspectives in Biology·Benjamin Swedlund, Fabienne Lescroart
Apr 11, 2018·Nature Communications·David J AndersonDavid A Elliott
Oct 18, 2018·Basic Research in Cardiology·Ingmar Sören Meyer, Florian Leuschner
Nov 7, 2019·Scientific Reports·Deevina ArasaratnamDavid A Elliott
Apr 24, 2019·Nature Biomedical Engineering·Haodong ChenJoseph C Wu
Mar 27, 2018·Current Opinion in Biotechnology·Joe Z ZhangJoseph C Wu
Jul 24, 2021·Stem Cell Reports·Chikako OkuboYoshinori Yoshida

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

Excel
GraphPad Prism

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