title: Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells.
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.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.|Li Dak-Sum Research Centre - HKU-Karolinska Institutet Collaboration on Regenerative Medicine, University of Hong Kong, Hong Kong, China.|Lau Ming-Wai Center for Regenerative Medicine, Karolinska Institutet, Hong Kong, China.|Department of Cell and Molecular Biology and Medicine, Karolinska Institute, Stockholm S-171 77, Sweden.
authors.forename: Boon-Seng
authors.initials: BS
authors.lastname: Soh
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
authors.forename: Shi-Yan
authors.initials: SY
authors.lastname: Ng
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.|Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Buac
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
authors.forename: Joo-Hye C
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Cell and Molecular Biology and Medicine, Karolinska Institute, Stockholm S-171 77, Sweden.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lian
authors.affiliation: Department of Cell and Molecular Biology and Medicine, Karolinska Institute, Stockholm S-171 77, Sweden.
authors.forename: Jiejia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cell and Molecular Biology and Medicine, Karolinska Institute, Stockholm S-171 77, Sweden.
authors.forename: Kylie S
authors.initials: KS
authors.lastname: Foo
authors.affiliation: Department of Cell and Molecular Biology and Medicine, Karolinska Institute, Stockholm S-171 77, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Felldin
authors.affiliation: Department of Cell and Molecular Biology and Medicine, Karolinska Institute, Stockholm S-171 77, Sweden.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: He
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street #02-01, Genome, Singapore 138672, Singapore.
authors.forename: Massimo
authors.initials: M
authors.lastname: Nichane
authors.affiliation: Cancer Institute of Singapore, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.|Li Dak-Sum Research Centre - HKU-Karolinska Institutet Collaboration on Regenerative Medicine, University of Hong Kong, Hong Kong, China.|Lau Ming-Wai Center for Regenerative Medicine, Karolinska Institutet, Hong Kong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bu
authors.affiliation: Li Dak-Sum Research Centre - HKU-Karolinska Institutet Collaboration on Regenerative Medicine, University of Hong Kong, Hong Kong, China.|Lau Ming-Wai Center for Regenerative Medicine, Karolinska Institutet, Hong Kong, China.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Li
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street #02-01, Genome, Singapore 138672, Singapore.
authors.forename: Bing
authors.initials: B
authors.lastname: Lim
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.|Department of Cell and Molecular Biology and Medicine, Karolinska Institute, Stockholm S-171 77, Sweden.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1