A Drug-Inducible System for Direct Reprogramming of Human Somatic Cells to Pluripotency

Dirk Hockemeyer, Frank Soldner, Elizabeth G. Cook, Qing Gao, Maisam Mitalipova, Rudolf Jaenisch

Research output: Contribution to journalArticle

244 Scopus citations

Abstract

Current approaches to reprogram human somatic cells to pluripotent iPSCs utilize viral transduction of different combinations of transcription factors. These protocols are highly inefficient because only a small fraction of cells carry the appropriate number and stoichiometry of proviral insertions to initiate the reprogramming process. Here we have generated genetically homogeneous "secondary" somatic cells, which carry the reprogramming factors as defined doxycycline (DOX)-inducible transgenes. These cells were obtained by infecting fibroblasts with DOX-inducible lentiviruses, isolating "primary" iPSCs in the presence of the drug, and finally differentiating to "secondary" fibroblasts. When "secondary" fibroblast lines were cultured in the presence of DOX without further viral infection, up to 2% of the cells were reprogrammed to pluripotent "secondary" human iPSCs. This system will facilitate the characterization of the reprogramming process and provides a unique platform for genetic or chemical screens to enhance reprogramming or replace individual factors.

Original languageEnglish (US)
Pages (from-to)346-353
Number of pages8
JournalCell Stem Cell
Volume3
Issue number3
DOIs
StatePublished - Sep 11 2008

Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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