De-Differentiation of Mouse Interfollicular Keratinocytes by the Embryonic Transcription Factor Oct-4

Abstract

The embryonic transcription factor Oct-4 is often referred to as the master regulator of the undifferentiated state. Although its role in maintaining embryonic stem (ES) cell pluripotency is well established, its ability to directly reprogram committed somatic cells is not well defined. Using transient transfection, we tested its ability to revert mouse interfollicular epidermal basal keratinocytes to a more ES cell-like state. We found that the Oct-4-transfected keratinocytes expressed the Oct-4 target genes, Sox-2, Nanog, undifferentiated transcription factor 1 (Utf1), and Rex-1. We also noted an increase in developmental potential caused by Oct-4, with the transfected cells able to differentiate into neuronal cells when exposed to neuroectodermal differentiation medium. Control-transfected keratinocytes were unable to respond to the medium, and remained as keratinocytes. These findings suggest that Oct-4 may be the master regulator of the pluripotent state and demonstrate that differentiated somatic cells can be reverted into more developmentally potent cells through the use of a single factor. The latter finding has great implications for therapeutic cell-replacement applications using cells from easily accessible adult tissues, such as the skin.

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

“…Bearing in mind the findings of the present study, it is also of interest to note that murine epidermal basal keratinocytes transiently transfected with Pou5f1 can differentiate into neuronal cells, suggesting that aberrant expression of Pou5f1 is sufficient for reverting differentiated somatic cells into more developmentally potent cells [41]. Also, the factors Pou5f1, Sox2, c-Myc and Klf4 can induce the reprogramming of murine fibroblasts into ESlike cells with activated endogenous Pou5f1 and Nanog expression [42,43].…”

Rat alveolar type I cells proliferate, express OCT-4, and exhibit phenotypic plasticity in vitro

“…OCT-4 is found in pluripotent stem cells of early embryos, where it is important in maintaining embryonic stem cell pluripotency. The striking observation that OCT-4-transfected keratinocytes could acquire characteristics of neuronal cells when exposed to the appropriate stimuli (22) appeared to confirm the concept that OCT-4 might be a "master regulator" of the pluripotent state, although OCT-4 by itself was not sufficient to induce pluripotency in fibroblasts (50). Recent experiments have shown that OCT-4 is a critical factor that can mediate, along with other factors, transformation of somatic cells to a stem cell phenotype (25,40,41).…”

Stem Cells and the Kidney

“…It is interesting that the cells express stem cell markers 5,6 It is interesting that induced expression of Oct-4 either alone or in combination with other stem cell transcription factors is sufficient to expand the differentiation potential of somatic cells. 7,8 An important finding of this study is the ability of injected CD24-and CD133-expressing cells to reconstitute the injured kidney and improve both structure and function. Cellular therapy in AKI has attracted much recent attention.…”

“…The article by Brunelli et al 8 is a retrospective, case-control study of patients undergoing outpatient colonoscopy at three University of Pennsylvania Health System affiliates. It compares patients who subsequently developed acute kidney injury (AKI) to those who maintained normal renal function.…”

“…Two large, observational, retrospective studies 8,9 in this issue of JASN aim to define that incidence and identify risk factors. The article by Brunelli et al 8 is a retrospective, case-control study of patients undergoing outpatient colonoscopy at three University of Pennsylvania Health System affiliates.…”