Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy

Nat Cell Biol. 2011 Mar;13(3):215-22. doi: 10.1038/ncb2164. Epub 2011 Jan 30.

Abstract

Here we show that conventional reprogramming towards pluripotency through overexpression of Oct4, Sox2, Klf4 and c-Myc can be shortcut and directed towards cardiogenesis in a fast and efficient manner. With as little as 4 days of transgenic expression of these factors, mouse embryonic fibroblasts (MEFs) can be directly reprogrammed to spontaneously contracting patches of differentiated cardiomyocytes over a period of 11-12 days. Several lines of evidence suggest that a pluripotent intermediate is not involved. Our method represents a unique strategy that allows a transient, plastic developmental state established early in reprogramming to effectively function as a cellular transdifferentiation platform, the use of which could extend beyond cardiogenesis. Our study has potentially wide-ranging implications for induced pluripotent stem cell (iPSC)-factor-based reprogramming and broadens the existing paradigm.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Culture Techniques*
  • Cell Differentiation
  • Cell Proliferation
  • Electrophysiology / methods
  • Fibroblasts / cytology*
  • Flow Cytometry
  • Induced Pluripotent Stem Cells / cytology
  • Mice
  • Microscopy, Fluorescence / methods
  • Myocytes, Cardiac / cytology*
  • Retroviridae / genetics
  • Time Factors
  • Transgenes

Substances

  • Calcium