(A) Schematic overview (left) of the two transplantation target sites in the adult mouse brain: (1) the cortex and (2) the hilus of the dentate gyrus. Six months after transplantation, an immunohistological analysis (right) revealed a sound survival rate of the GFP-labeled iNSCs in both regions. Image 1 displays a maximum intensity projection (MIP). Red dashed lines indicate the hippocampus.

(B) iNSC-derived cells do not express the cell-cycle marker KI67 (upper panel) or the neural progenitor marker DCX (lower panel). The images represent the MIPs of a confocal z stack.

(C and D) iNSCs at graft edges or those that had substantially migrated outside of the graft differentiate into TUJ1- (C) and NEUN-positive (D) neurons and showed an orientation and shape comparable with the neighboring endogenous neurons when transplanted into the cortex.

(E and F) Transplanted iNSCs of the hilus migrate and integrate into the granule layer of the dentate gyrus and express the neuronal maker TUJ1 (E) and NEUN (F). Dashed lines indicate the regions of magnification.

(G) iNSC-derived NEUN-positive cells transplanted into the hilus integrated into the existing network and extended the CA3 region of the hippocampus. Dashed lines indicate the region of magnification.

(H) In both regions, iNSCs differentiated into the glial lineage indicated via the astrocyte marker GFAP (upper panel; MIP of a confocal z stack) and the oligodendrocyte marker OLIG2 (lower panel; the left image represents a MIP of a confocal z stack).