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

3 years ago

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

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.

Graphical abstract

Teaser

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.

Publisher URL: www.sciencedirect.com/science

DOI: S2213671117304198