Analysis of transcriptional regulation of cell reprogramming and
development of practical systems of cell differentiation.
Induced pluripotent stem (iPS) cells can be produced by introducing several genes into mature somatic cells. These cells are expected to be useful for many applications including regenerative medicine. However, the mechanisms of the cell reprogramming remain largely unknown. Their understanding is expected not only to enable more efficient production of iPS cells but also to give us important information about the maintenance of the undifferentiated status and the orderly differentiation of these cells. In conventional methods of iPS cell production, we usually infect four retroviral vectors expressing reprogramming factors (Oct4, Sox2, Klf4 and c-myc) each other. But, because their expression balance can not be controlled, the quality variation of iPS cells is serious problem for efficient production of iPS cells and analysis of its mechanism.
We developed “Persistent RNA vector (SeVdp vector)” which is capable of sustained expression of multiple transgenes without chromosomal integration. This vector can produce transgene-free iPS cells more efficiently than conventional methods (Nishimura, K. et al. 2011). Such a novel methods could establish various iPS cells from many types of tissue cells in our collaborators (Nishimura, T. et al 2013, Takayama, N. et al 2010).
Using these methods, we try to investigate molecular mechanism of cell reprogramming. These analyses will make us enable to establish methods of more efficient production of safe iPS cells. Moreover, we also apply persistent RNA vectors to obtain safe differentiated tissue cells efficiently. Taken together, these researches will contribute great progress of medical application of regenerative medicine, from iPS cell production to preparation of differentiated tissue.
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Theme
---Analysis for transcriptional regulation on early stage of iPS cell production
---Analysis for quality control and epigenetic regulation on iPS cells
---Establishment of safe differentiation system by using persistent RNA vector