Generation of induced pluripotent stem cells by using a mammalian artificial chromosome expression system

Anna Tóth, Katalin Fodor, P. Blazsó, I. Cserpán, Tünde Praznovszky, V. Tubak, A. Udvardy, Gy Hadlaczky, R. Katona

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Direct reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPS) was achieved recently by overexpression of four transcription factors encoded by retroviral vectors. Most of the virus vectors, however, may cause insertional mutagenesis in the host genome and may also induce tumor formation. Therefore, it is very important to discover novel and safer, non-viral reprogramming methods. Here we describe the reprogramming of somatic cells into iPS cells by a novel protein-based technique. Engineered Oct4, Sox2 and Klf4 transcription factors carrying an N-terminal Flag-tag and a C-terminal polyarginine tail were synthesized by a recently described mammalian artificial chromosome expression system (ACEs). This system is suitable for the high-level production of recombinant proteins in mammalian tissue culture cells. Recombinant proteins produced in this system contain all the post-translational modifications essential for the stability and the authentic function of the proteins. The engineered Oct4, Sox2 and Klf4 proteins efficiently induced the reprogramming of mouse embryonic fibroblasts by means of protein transduction. This novel method allows for the generation of iPS cells, which may be suitable for therapeutic applications in the future.

Original languageEnglish
Pages (from-to)331-345
Number of pages15
JournalActa biologica Hungarica
Volume65
Issue number3
DOIs
Publication statusPublished - Sep 1 2014

Keywords

  • Artificial Chromosome Expression system
  • cell and gene therapy
  • iPS cell
  • reprogramming
  • reprogramming proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Neurology

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