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Table 4 All studies used transcription factors and small molecules to reprogram human fibroblasts into NSCs and NPCs

From: How to reprogram human fibroblasts to neurons

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 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 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 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