Table 4 All studies used transcription factors and small molecules to reprogram human fibroblasts into NSCs and NPCs
| Target cell type | Reprogramming factors | Reprogramming mechanism | Effects on neural cells induction | Morphogens or small molecules | Reprogramming mechanism | Effects on neural cells induction | References |
|---|---|---|---|---|---|---|---|
| NPCs | SOX2 | OCT3/4 and NANOG activation | Play a key role in the early stages of neurogenesis and the process of reprogramming cells to a pluripotent state; associated with multipotent and unipotent stem cells | Valproic acid | Unknown | Unknown | Maucksch et al. 2012 [109] |
| PAX6 | Concentration-dependent NGN2 activation, HES1 inhibition |
Play a key role in the early stages of neurogenesis; be essential for neural stem cell proliferation, multipotency and neurogenesis; involve neural lineage determination SOX2 and PAX6 work together can reprogram human fibroblasts into neural precursor cells | |||||
| NPCs | OCT4, SOX2, KLF4, MYC | Unknown | Unknown | SB431542 | TGFβ inhibition | Unknown | Lu et.al. 2013 [68] |
| CHIR99021 | GSK3β inhibition | Render neural progenitors in the entire neuraxis in a state of self-renewal | |||||
| NSCs | OCT4, | PAX6 activation, H3K27me3 inhibition | Unknown | A83-01 | TGFβ inhibition | Unknown | Zhu et.al. 2014 [110] |
| CHIR99021 | GSK3β inhibition | ||||||
| Sodium butyrate | HDAC inhibition | ||||||
| Lysophosphatidic acid | Unknown | ||||||
| Rolipram | PDE4 inhibition | ||||||
| SP600125 | JNK inhibition | ||||||
| NPCs | OCT4, SOX2,KLF4, C-MYC | Unknown | Unknown | CHIR99021, SB431542 | Unknown | Unknown | Meyer et al. 2015 [111] |
| NSCs | ZFP521 | Unknown | Unknown | CHIR99021, SB431542 | Unknown | Unknown | Shahbazi et al. 2016 [65] |
| NSCs | hOCT3/4-shp53-F | Unknown | Unknown | Y-27632 | Unknown | Unknown | Azmitia et.al. 2018 [112] |
| NSCs | BRN2, KLF4, SOX2, ZIC3 | Unknown | Have the ability of NSCs population maintenance and positive regulation of NPCs proliferation, induce neural crest identity of brain development and head development and the regional identity of a dorsal anterior hindbrain fate | CHIR99021 | GSK-3 inhibition | Unknown | Thier et al., 2019 [113] |
| ALK5 inhibitor II | ALK5 inhibition | ||||||
| Purmorphamine | Hedgehog-smoothened agonist | ||||||
| Tranylcypromine | Inhibitior of monoamine oxidase and CYP2 enzymes: A6; C19; and D6 | ||||||
| NSCs | SOX2 | Unknown | Unknown | CHIR99021 | Potent and selective GSK-3 inhibition | Unknown | Yanying et al. 2020 [114] |
| A83-01 |
Potent inhibition of TGF-β type I receptor ALK5 kinase, type I Activin/Nodal receptor ALK4 and type I nodal receptor ALK7 | ||||||
| RG108 | Non-nucleoside DNA methyltransferase inhibition | ||||||
| Parnate | Iirre-versible inhibition of lysine-specific demethylase 1 and monoamine oxidase | ||||||
| SMER28 | Positive regulator of autophagy | ||||||
| Hh-Ag 1.5 | Potent Hedgehog pathway Smo agonist | ||||||
| Retinoic acid | Endogenous agonist for retinoic acid receptors and retinoid X receptor | ||||||
| LDN193189 | Cell permeable BMP signaling inhibition |