Figure 1.
A diagram illustrates the reprogramming of somatic fibroblasts into induced neurons (iNs) or induced neural stem cells (iNSCs) in vitro by forced expression of transcription factors (TFs).
Fibroblasts can be transdifferentiated into iNs expressing microtubule-associated protein 2 (MAP2), a neuronal specific nuclear protein (NeuN), neuron-specific class III beta-tubulin (Tuj1), and doublecortin (DCX) by transduction of transcription factors brain-2 (Brn2, also known as Pou3f2), achaete-scute complex-like 1 (Ascl1), myelin transcription factor (Myt1l), and NeuroD1. iNs can be further specified to become different phenotypes, such as motor neurons expressing vesicular acetylcholine transporter (vChAT) and homeobox Bb9 (Hb9), or dopamine neurons expressing tyrosine hydroxylase (TH), the vesicular monoamine transporter 2 (VMAT2), dopamine transporter (DAT), aldehyde dehydrogenase 1 A1 (ALDH1A1), and calbindin. Similarly, fibroblasts can be reprogrammed into iNSCs expressing nestin and sex determining region Y-box 2 (Sox2) by transduction of transcription factors Sox2, Kruppel-like factor 4 (Klf4), myelocytomatosis viral oncogene homolog (c-Myc), Brn4/Pou3f4, and transcription factor 3 (E47/Tcf3). iNSCs can be further differentiated into neurons expressing MAP2, NeuN, Tuj1 and DCX, astrocytes expressing glial fibrillary acidic protein (GFAP) and CD44, and oligodendrocytes expressing galactocerebroside (GalC) and oligodendrocyte marker O4.