earticle

영어

Neural stem cells (NSCs) are self-renewing tripotent cell populations and have capacity of neuronal (neurons) and glial (astrocytes and oligodendrocytes) differentiation. Many researchers have reported that NSCs have therapeutic effects in neurological disease by transplantation. However, it is not easy to obtain NSCs in vitro. Recently, Yamanaka and colleagues showed that somatic cells could be reprogrammed into pluripotent state by enforcing reprogramming factors. Induced pluripotent stem (iPS) cells undergo unlimited self-renewal and have differentiation potential into various types of cells like embryonic stem cells. Direct differentiation into a specialized cell types from iPS cells hold considerable promise for regenerative medicine as well as basic research. Here, we induced differentiation of iPS cells into NSCs in vitro and in vivo, which were compared with embryonic stem (ES) cell-derived NSCs and brain derived NSCs. NSCs from ES and iPS cells were morphologically indistinguishable from brain derived NSCs and stained positive for NSCs markers Nestin and Sox2. ES cells derived NSCs were transcriptionally distinguishable from brain derived NSCs. However, global gene expression pattern were similar but distinct between iPS derived NSCs and brain derived NSCs. Moreover, iPS derived NSCs were spontaneously aggregated upon passaging, formed ES cell like colonies, and finally reactivated Oct4-GFP. The spontaneously reverted GFP-positive cells (iPS-NSC-iPS) expressed similar levels of pluripotency markers (Oct4,Nanog) to ES and iPS cells, and could form germ line chimera. One possible explanation for this phenomenon is that spontaneously re-reprogramming was associated with transgene re-activation when iPS cells were differentiated into NSCs. However, NSCs from dox-inducible iPScells could not be reprogrammed into pluripotent state without doxycycline. Taken together, iPS derived NSCs were morphologically and similar to brain derived NSCs, but differ in gene expression pattern and maintenance. * This work was supported by the Next Generation Bio-Green21 Program funded by the Rural Development Administration (Grant PJ008009).