title: The combination of Tet1 with Oct4 generates high-quality mouse-induced pluripotent stem cells.
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.
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China; National Institute of Biological Sciences, NIBS, Beijing, People's Republic of China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Chen
authors.forename: Yawei
authors.initials: Y
authors.lastname: Gao
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hailin
authors.initials: H
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011518:Proto-Oncogene Proteins; C540839:TET1 protein, mouse
keywords: DNA demethylation; Induced pluripotent stem cells; Pluripotency; Tet1