Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1

Nature. 2011 Jun 8;474(7350):225-9. doi: 10.1038/nature10106.

Abstract

Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf4. However, the conversion to iPSCs is inefficient. The proto-oncogene Myc enhances the efficiency of iPSC generation by OSK but it also increases the tumorigenicity of the resulting iPSCs. Here we show that the Gli-like transcription factor Glis1 (Glis family zinc finger 1) markedly enhances the generation of iPSCs from both mouse and human fibroblasts when it is expressed together with OSK. Mouse iPSCs generated using this combination of transcription factors can form germline-competent chimaeras. Glis1 is enriched in unfertilized oocytes and in embryos at the one-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, Essrb and the mesenchymal-epithelial transition. These results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Cellular Reprogramming*
  • DNA-Binding Proteins / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Epithelial-Mesenchymal Transition
  • Female
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism*
  • Gene Expression Profiling
  • Genes, myc / genetics
  • Hepatocyte Nuclear Factor 3-beta / metabolism
  • Homeodomain Proteins / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Nanog Homeobox Protein
  • Nuclear Transfer Techniques
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding
  • RNA-Binding Proteins / metabolism
  • Receptors, Estrogen / metabolism
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Esrrb protein, mouse
  • Foxa2 protein, mouse
  • GLIS1 protein, human
  • Glis1 protein, mouse
  • Homeodomain Proteins
  • Lin-28 protein, mouse
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • RNA-Binding Proteins
  • Receptors, Estrogen
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta

Associated data

  • GEO/GSE26431