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Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells

Boon-Seng Soh, Shi-Yan Ng, Hao Wu, Kristina Buac, Joo-Hye C. Park, Xiaojun Lian, Jiejia Xu, Kylie S. Foo, Ulrika Felldin, Xiaobing He, Massimo Nichane, Henry Yang, Lei Bu, Ronald A. Li, Bing Lim and Kenneth R. Chien ()
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Boon-Seng Soh: Cardiovascular Research Center, Massachusetts General Hospital
Shi-Yan Ng: Harvard University
Hao Wu: Cardiovascular Research Center, Massachusetts General Hospital
Kristina Buac: Cardiovascular Research Center, Massachusetts General Hospital
Joo-Hye C. Park: Cardiovascular Research Center, Massachusetts General Hospital
Xiaojun Lian: Karolinska Institute
Jiejia Xu: Karolinska Institute
Kylie S. Foo: Karolinska Institute
Ulrika Felldin: Karolinska Institute
Xiaobing He: Karolinska Institute
Massimo Nichane: Stem Cell and Developmental Biology, Genome Institute of Singapore
Henry Yang: Cancer Institute of Singapore, National University of Singapore
Lei Bu: Cardiovascular Research Center, Massachusetts General Hospital
Ronald A. Li: Li Dak-Sum Research Centre - HKU-Karolinska Institutet Collaboration on Regenerative Medicine, University of Hong Kong
Bing Lim: Stem Cell and Developmental Biology, Genome Institute of Singapore
Kenneth R. Chien: Harvard University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Coronary arteriogenesis is a central step in cardiogenesis, requiring coordinated generation and integration of endothelial cell and vascular smooth muscle cells. At present, it is unclear whether the cell fate programme of cardiac progenitors to generate complex muscular or vascular structures is entirely cell autonomous. Here we demonstrate the intrinsic ability of vascular progenitors to develop and self-organize into cardiac tissues by clonally isolating and expanding second heart field cardiovascular progenitors using WNT3A and endothelin-1 (EDN1) human recombinant proteins. Progenitor clones undergo long-term expansion and differentiate primarily into endothelial and smooth muscle cell lineages in vitro, and contribute extensively to coronary-like vessels in vivo, forming a functional human–mouse chimeric circulatory system. Our study identifies EDN1 as a key factor towards the generation and clonal derivation of ISL1+ vascular intermediates, and demonstrates the intrinsic cell-autonomous nature of these progenitors to differentiate and self-organize into functional vasculatures in vivo.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10774

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DOI: 10.1038/ncomms10774

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