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, Kenneth R. Chien

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12 Scopus citations

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.

Original languageEnglish (US)
Article number10774
JournalNature communications
Volume7
DOIs
StatePublished - Mar 8 2016

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Soh, B. S., Ng, S. Y., Wu, H., Buac, K., Park, J. H. C., Lian, X., Xu, J., Foo, K. S., Felldin, U., He, X., Nichane, M., Yang, H., Bu, L., Li, R. A., Lim, B., & Chien, K. R. (2016). Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells. Nature communications, 7, [10774]. https://doi.org/10.1038/ncomms10774