title: Conversion of human fibroblasts to angioblast-like progenitor cells.
abstract: Lineage conversion of one somatic cell type to another is an attractive approach for generating specific human cell types. Lineage conversion can be direct, in the absence of proliferation and multipotent progenitor generation, or indirect, by the generation of expandable multipotent progenitor states. We report the development of a reprogramming methodology in which cells transition through a plastic intermediate state, induced by brief exposure to reprogramming factors, followed by differentiation. We use this approach to convert human fibroblasts to mesodermal progenitor cells, including by non-integrative approaches. These progenitor cells demonstrated bipotent differentiation potential and could generate endothelial and smooth muscle lineages. Differentiated endothelial cells exhibited neo-angiogenesis and anastomosis in vivo. This methodology for indirect lineage conversion to angioblast-like cells adds to the armamentarium of reprogramming approaches aimed at the study and treatment of ischemic pathologies.
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Kurian
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sancho-Martinez
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nivet
authors.forename: Aitor
authors.initials: A
authors.lastname: Aguirre
authors.forename: Krystal
authors.initials: K
authors.lastname: Moon
authors.forename: Caroline
authors.initials: C
authors.lastname: Pendaries
authors.forename: Cecile
authors.initials: C
authors.lastname: Volle-Challier
authors.forename: Francoise
authors.initials: F
authors.lastname: Bono
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
authors.forename: Julian
authors.initials: J
authors.lastname: Pulecio
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.forename: Mo
authors.initials: M
authors.lastname: Li
authors.forename: Nuria
authors.initials: N
authors.lastname: Montserrat
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruiz
authors.forename: Ilir
authors.initials: I
authors.lastname: Dubova
authors.forename: Concepcion
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Ahmet M
authors.initials: AM
authors.lastname: Denli
authors.forename: Francesca S
authors.initials: FS
authors.lastname: Boscolo
authors.forename: Rathi D
authors.initials: RD
authors.lastname: Thiagarajan
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Jeanne F
authors.initials: JF
authors.lastname: Loring
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger