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

Abstract

SummaryMammalian 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.

Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming

“…Additionally, consistently with previous report of vimentin‐deficient fibroblasts exhibiting a slower rate of proliferation, fibroblasts isolated from the arm skin, along with fibroblasts from neck and breast regions, all mostly vimentin‐positive, proliferated at significantly higher rate than dermal fibroblasts from abdomen or thigh that showed a reduced expression of vimentin (Figure ). Notably, accumulating evidence suggests that low proliferation rates of somatic cells enhance their reprogramming, hence difference in proliferation rate of fibroblasts isolated from different anatomic sites might indirectly suggest a diverse response of fibroblast populations to reprogramming. Despite the common expression of several transcripts of genes typically expressed in mesenchymal cells, there was a heterogeneous expression of CD105 and CD146 when comparing dermal fibroblasts obtained from distinct anatomic sites, with fibroblasts isolated from abdomen skin that had a higher expression of all three markers.…”

Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress

“…In our previous study, by mining proteomic data of preimplantation embryos, we found that several maternal factor candidates can facilitate somatic cell reprogramming. 10 In the present study, we aimed to explore the function and mechanism of one of the maternal factors, Surf4, in somatic cell reprogramming. We employed a secondary reprogramming system based on the drug‐inducible expression of the four Yamanaka factors (Figure S1 A).…”

“… 7 , 8 We previously found that some oocyte‐enriched proteins identified through mass spectrometry 9 can enhance somatic cell reprogramming. 10 In this study, we further explored the function and mechanism of Surf4 , which is one of these maternal factors.…”

Characterization of DNA Methylation Patterns and Mining of Epigenetic Markers During Genomic Reprogramming in SCNT Embryos

“…Among them, Kdm5b, Zscan5b, and members of the zinc finger family proteins (Zfp217, Zfp574, Zfp662, Zfp809, and Zfp868) all work as reprogramming promotion factors. Tead4, Obox6, and Yy1 are key transcription factors involved in regulation of pluripotency ( Sakurai et al, 2017 ; Wu et al, 2017 ; Hu et al, 2019 ; Schiebinger et al, 2019 ). Dppa4 is a pluripotency-related factor during early development ( Hernandez et al, 2018 ).…”