Haematopoietic Stem Cell Laboratory, Cancer Research UK, London, UK.
Cytotherapy. 2012 Oct;14(9):1054-63. doi: 10.3109/14653249.2012.697145. Epub 2012 Jul 2.
The identification of mesenchymal stromal cells (MSC) from bone marrow by Friedenstein et al. dates back to 1970, but many questions remain unanswered about the biology of these cells. MSC have a wide clinical application because of their differentiation capacity and immunosuppressive properties. They are capable of self-renewal; however, the mechanism is poorly understood. The embryonic transcription factor Octamer binding transcription factor 4 (Oct4) has been suggested as an indicator of multipotency for mouse MSC. OCT4 has also been studied extensively for its involvement in self-renewal of embryonic stem cells and in cancer cells.
Using a lentiviral-inducible vector, we modulated OCT4 expression in human MSC and studied its effect on the biology of these cells.
Surprisingly, we found that the overexpression of OCT4 induced early senescence, as evidenced by increased expression of P14 and P16(INK4A) in MSC.
These results indicate a differential role for exogenously expressed human OCT4 in adult and embryonic systems.
弗赖登斯坦等人于 1970 年从骨髓中鉴定出间充质基质细胞（MSC），但这些细胞的生物学特性仍有许多未解之谜。MSC 具有分化能力和免疫抑制特性，临床应用广泛。它们具有自我更新的能力；然而，其机制尚不清楚。胚胎转录因子八聚体结合转录因子 4（Oct4）被认为是小鼠 MSC 多能性的指标。OCT4 也因其参与胚胎干细胞和癌细胞的自我更新而被广泛研究。
我们使用慢病毒诱导载体调节人 MSC 中的 OCT4 表达，并研究其对这些细胞生物学特性的影响。
令人惊讶的是，我们发现 OCT4 的过表达诱导了 MSC 的早期衰老，这表现在 P14 和 P16(INK4A)的表达增加。
这些结果表明，外源性表达的人 OCT4 在成人和胚胎系统中发挥不同的作用。
