Abstract
Cell type conversion by genetic reprogramming is ubiquitously observed in neoplasia and also in non-tumor cells under pathological condition. Although mechanisms, by which a cell converts, has remained to be resolved, the conditions for critical transcriptional switching must be the central issue. On the other hand, the regenerative cell or ESC therapy becomes more and more important to treat a vast diseases, such as Parkinson's disease, spinal cord injury, and diabetes. However, the ethical difficulty and the tissue rejection problem are main obstacles against the use of ESC. The generation of the differentiated or pluripotent cells from the patients' own cells by the conversion is one way to circumvent the problems. We attempted and partly succeeded to transdifferentiate or dedifferentiate mouse fibroblast cell line Balb3T12/3 into skeletal muscle, neuron-like cell, and stem-cell-like cell, when MyoD, neurogenin, and Nanog cDNA were forcibly expressed respectively. The differentiated cell fates were identified by detecting the expression of skeletal myosin and L-type Ca channel, MAP2, and alkaline phosphatase and specific morphology respectively with immunocytochemical and electrophysiological methods. Further the transdifferentiation into muscle or neuron-like cell was quantitatively facilitated with histone deacetylase inhibitor, chromatin configulation modifier. While, Nanog expression dedifferentiated the fibroblast into stem cell like, providing the possibility for multidirectional cell type conversation. [J Physiol Sci. 2007;57 Suppl:S133]
