The combination of Tet1 with Oct4 generates high-quality mouse-induced pluripotent stem cells

Stem Cells. 2015 Mar;33(3):686-98. doi: 10.1002/stem.1879.

Abstract

The DNA dioxygenase Tet1 has recently been proposed to play an important role in the reprogramming of somatic cells to pluripotency. Its oxidization product 5-hydroxymethylcytosine, formerly considered an intermediate in the demethylation of 5-methylcytosine, has recently been implicated as being important in epigenetic reprogramming. Here, we provide evidence that Tet1 (T) can replace multiple transcription factors during somatic cell reprogramming and can generate high-quality mouse induced pluripotent stem cells (iPSCs) with Oct4 (O). The OT-iPSCs can efficiently produce viable mice derived entirely from iPSCs through tetraploid complementation; all 47 adult OT-iPSC mice grew healthily, without tumorigenesis, and had a normal life span. Furthermore, a new secondary reprogramming system was established using the OT all-iPSC mice-derived somatic cells. Our results provide the first evidence that the DNA dioxygenase Tet1 can replace multiple pluripotency transcription factors and can generate high-quality iPSCs with Oct4.

Keywords: DNA demethylation; Induced pluripotent stem cells; Pluripotency; Tet1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cellular Reprogramming Techniques / methods*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • Pregnancy
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism

Substances

  • DNA-Binding Proteins
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Proto-Oncogene Proteins
  • TET1 protein, mouse