Figure 1.

Schematic demonstrating basic cell types and gene expression generated by Sox2-mediated reprogramming of fibroblasts compared with in vivo lineage of embryonic stem cells. (A): In vivo ESCs undergo neural induction where pluripotency genes OCT4 and NANOG are downregulated and NSC markers SOX1, SOX2, and SOX3 are expressed. The neural tube becomes regionalized by expression of patterning genes, including PAX6, OTX2, and EN1, in a rostral/caudal and dorsal/ventral manner. Domains are further subdivided by heterogeneous expression of transcription factors, for example ACHL1, OLIG2, NGN2, and DLX2, in the forebrain. NPCs go on to generate astrocytes, oligodendrocytes, and multiple neuronal types depending on the region of origin of the cell. (B): Direct reprogramming using Sox2 combined with other transcription factors in a defined reprogramming medium can generate iNSCs/iNPCs with gene expression patterns that are similar to those of in vivo-derived NSCs or NPCs while no longer expressing fibroblast genes. Induced NSCs/NPCs can be differentiated into cells expressing markers for astrocytes, oligodendrocytes, and neurons of multiple subtypes. Abbreviations: ESC, embryonic stem cell; iNPC, induced neural precursor cell; iNSC, induced neural stem cell; iPSC, induced pluripotent stem cell; NPC, neural precursor cell; NSC, neural stem cell.