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Stem cells (Dayton, Ohio)

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


PMID 25331067

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.