Study of differentiation of apoptosis-resistant nerve stem cells and their application to neuroregeneration

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First we examined the development of neurons in Apaf1- and Bc1-XL-doubly knockout embryos. In the doubly-knockout mice, there was accumulation of neurons just as in Apaf1-single knockout embryos. However, differentiation of nerve stem cells into mature neurons was normal in both Apaf1-single and doubly knockout mice. Next we demonstrated BMP2drives the differentiation f nerve stem cells into astrocytes. Practically, BMP2 suppresses the differentiation of stem cells into neurons by the induction of inhibitory HLH factors and the resultant suppression of bHLH transcription factors that favor nerve differentiation. In regeneration of therapies of nerve/spine, it is a serious problem that transplanted stem cells tend to differentiate into astorocytes. Another problem will be the poor viability of transplanted stem cells in the host. Since Apaf1-deficient stem cells are resistant to various apoptotic stimuli while showing normal differentiation into neurons, our results may shed light to the development of novel neuroregenerative therapies by driving the differentiation of apoptosis-resistant stem cells arbitrarily into neurons