Journal
STEM CELL REPORTS
Volume 9, Issue 5, Pages 1692-1705Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.09.012
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Funding
- National Natural Science Foundation of China [31430056, 31501183, 31371512, 81322029, 31721003]
- Ministry of Science and Technology of China [2016YFA0100400]
- Shanghai Subject Chief Scientist Program [15XD1503500]
- Chenguang Program from the Shanghai Education Development Foundation [15CG19]
- Shanghai Municipal Education Commission
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Mammalian oocytes possess fascinating unknown factors, which can reprogram terminally differentiated germ cells or somatic cells into totipotent embryos. Here, we demonstrate that oocyte-specific homeobox 1 (Obox1), an oocyte-specific factor, can markedly enhance the generation of induced pluripotent stem cells (iPSCs) from mouse fibroblasts in a proliferation-independent manner and can replace Sox2 to achieve pluripotency. Overexpression of Obox1 can greatly promote mesenchymal-to-epithelial transition (MET) at early stage of OSKM-induced reprogramming, and meanwhile, the hyperproliferation of THY1-positive cells can be significantly mitigated. Subsequently, the proportion of THY1-negative cells and Oct4-GFP-positive cells increased dramatically. Further analysis of gene expression and targets of Obox1 during reprogramming indicates that the expression of Obox1 can promote epithelial gene expression and modulate cell-cycle-related gene expression. Taken together, we conclude that the oocyte-specific factor Obox1 serves as a strong activator for somatic cell reprogramming through promoting the MET and mitigating cell hyperproliferation.
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