Oocyte-Specific Homeobox 1, Obox1, Facilitates Reprogramming by Promoting Mesenchymal-to-Epithelial Transition and Mitigating Cell Hyperproliferation

Abstract

Summary: 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. : Mammalian oocytes possess unknown factors, which can reprogram differentiated cells into totipotent embryos and thereafter give rise to a new organism. In this article, Gao and colleagues found that Obox1, an oocyte factor, can enhance somatic cell reprogramming to iPSCs by promoting mesenchymal-to-epithelial transition and mitigating cell hyperproliferation. Keywords: oocyte factor, reprogramming, mesenchymal-to-epithelial transition, hyperproliferation, iPSCs, cell cycle, M phase, Obox1