Fig. 7

Proposed model for reprogramming for iNPCs and differentiation for specific lineages of neurons. Combination of Yamanaka Factors (Oct4, Sox2, Klf4, c-Myc) and ESC media leads to iPSC dedifferentiation from somatic cells (Path 1). Direct conversion of somatic cells into iNPCs was achieved by transducing fibroblasts or astrocytes with NPC fate determinants (Path 2). Induced neurons are termed after terminally differentiated cells were directly converted into neurons (Path 4). We propose that somatic cells can be converted to regional-committed iNPCs with restricted neuronal subtype differentiation capacities (e.g. glutamatergic and GABAergic neurons for telencephalon). The transdifferentiation is achieved using NPC fate master regulators (e.g., Sox2 and Brn2) in addition to potent regional determinants (e.g. Foxg1 for telencephalon) (Path 3). The differentiation potential of AiNPC differentiation towards forebrain Gluamatergic and GABAergic neurons can be altered by the forced expression of TFs that promotes dedicated neuronal specifications (e.g., Lhx8 for cholinergic neurons and Foxa2/Lmx1a for midbrain dopaminergic neurons)