Figure 1.

Comparison of direct and indirect reprogramming to the neuronal cell-fate. Somatic cells from humans or mice can be directly or indirectly reprogrammed to neurons. Direct reprogramming can be achieved by overexpressing Brn2, Ascl1, and Myt1L (BAM factors) which reprogram somatic cells within 32 days by activating neuronal networks involved in neurogenesis and neuronal differentiation. In contrast, somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) with the Yamanaka factors (Oct4, Sox2, c-Myc, and Klf4). Reprogramming to the intermediate iPSC state extends the reprogramming timeline as quality control assays for karyotypic stability and pluripotency must be conducted. Overexpression of the BAM factors or supplemental neurogenesis factors, such as, Ngn2 or NeuroD1 are sufficient to differentiate iPSCs to neurons. Induced and IPSC-derived neurons are characterized based on morphology, pan-neuronal and subtype markers, and functional properties.