Conversion of human fibroblasts to angioblast-like progenitor cells

Leo Kurian, Ignacio Sancho-Martinez, Emmanuel Nivet, Aitor Aguirre, Krystal Moon, Caroline Pendaries, Cecile Volle-Challier, Francoise Bono, Jean-Marc Herbert, Julian Pulecio, Yun Xia, Mo Li, Nuria Montserrat, Sergio Ruiz, Ilir Dubova, Concepcion Rodriguez, Ahmet M Denli, Francesca S Boscolo, Rathi D Thiagarajan, Fred H GageJeanne F Loring, Louise C Laurent, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

136 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)77-83
Number of pages7
JournalNATURE METHODS
Volume10
Issue number1
Early online date2 Dec 2012
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Animals
  • Biomarkers
  • Blotting, Western
  • Cell Differentiation
  • Cell Lineage
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Reprogramming
  • Endothelium, Vascular
  • Fibroblasts
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Mice
  • Myocytes, Smooth Muscle
  • Neovascularization, Physiologic
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells

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