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Table 2 Reprogramming human fibroblasts into neurons using small molecules since 2012

From: How to reprogram human fibroblasts to neurons

Target Cell Type Morphogens or Small molecules Reprogramming Mechanism Effects on neural cells induction Reprogramming factors Effects on neural cells induction References
Neurons CHIR99021 GSK3β inhibition Suit the branch of neurons’ and axons’ growth ASCL1, NGN2 Improve positive rate of Tuj1+ cells Ladewig et al. 2012 [20]
SB431542 ALK5 inhibition (Activin/Nodal/TGFβ pathway inhibition) Unknown   
NOGGIN, LDN-193189 ALK2/3/6 inhibition (BMP/SMAD signaling inhibition Unknown   
Cholinergic neurons Forskolin cAMP activation Induce massive production of Tuj1+ cells, which have neuron-like morphology NGN2/NGN2+ Activate a cohesive pathway that determines a more homogenous neuronal subtype (cholinergic neuron) Liu et al. 2013 [50]
Dorsomorphin BMP inhibition Promote neuron survival and maturation cooperating with FSK, while DM itself does not affect neuron transformation SOX11+ Promote the survival and maturation of neurons but does not specify the neuron subtype
    FGF2 Improve reprogramming efficiency significantly
Neurons NOGGIN TGFβ inhibition Unknown NGN2-2A-ASCL1 Unknown Mertens et al. 2015 [101]
LDN193189, SB431542, A83-01 ALK2/3/4/5/7 inhibition  
CHIR99021, GSK3β inhibition,
Forskolin, DBcAMP cAMP activation
Glutamatergic neurons Valproic acid HDAC inhibition Activate cells through epigenetic modification Hu et al. 2015 [22]
CHIR99021 GSK3β inhibition Promote the transformation of human fibroblasts to neurons and induce dopamine neurons to human ESCs
Repsox TGFβ inhibition Improve neuron survival
Forskolin cAMP activation Enable Ngn2 to convert human fibroblasts into cholinergic neurons
SP600125 JNK inhibition Facilitate the neural reprogramming of AHDF transduced with OCT4 alone
G06983 PKC inhibition Improve human pluripotent stem cells and induces neuritogenesis of Neuro-2a cells
Y-27632 ROCK inhibition Maintain the viability of pluripotent stem cells and neurons
Dorsomorphin BMP inhibition Promote the survival and maturation of neurons
Motor neurons Forskolin Dorsomorphin Unknown All increase the population of Tuj1+ cells reprogramming from fibroblasts NGN2-IRES-GFP-T2A-SOX11, ISL1-T2A-LHX3 Unknown Liu et al. 2016 [92]
GABAergic Neurons CHIR99021, SB431542, Db-cAMP Unknown Improve the efficiency of neuron differentiation Order PTB knockdown and nPTB knockdown Induce the transcription of miR-9, the activation of miR-9 made the induced neuron-like cells progress to functional neurons Xue et al. 2016 [53]
PTB knockdown and BRN2 expression Facilitate the expression of MAP2 in neurons and promote the influx of Ca2+
Neurons Kenpaullone (WL12) GSK3β inhibition Increase reprogramming efficiency ASCL1, BRN2, MYT1L Unknown Pfisterer et al. 2016 [55]
PGE2 cAMP/PKA modulator Increase reprogramming efficiency
Forskolin cAMP activation Unknown
BML 210 HDAC inhibition Facilitate the recovery of pluripotency in reprogramming
Aminoresveratrol Sulfate (EL38) SIRT1 activation Unknown
PP2 Src kinase inhibition Skip the SOX2 pathway, activate sirtuins complement and promote Klf4 expression
Neurons CHIR99021, SB431542, NOGGIN, LDN193189, Valproic acid Unknown Unknown ASCL1, BRN2 Unknown Drouin-Ouellet et al. 2017 [102]
Shrigley et al. 2018 [103]
Marina et al. 2020 [56]
SHREST miR-9 activation, miR-124 activation
Motor neurons Kenpaullone GSK3β inhibition; HPK1 / GCK-like kinase inhibition Enhance the binding of other small molecules to its target Qin et al. 2018 [7]
Later change to CHIR99021 cAMP activation Promote the growth of neurons, which is weaker than that of Kenpaullone
Forskolin ROCK inhibition Unknown
Y27632 Unknown Unknown
Purmorphamine Unknown Unknown
RA Unknown Improve the differentiation from pluripotent stem cells to motor neurons through the activation of RA and SHH signals
Neurons Valproic acid Unknown Unknown Wan et al. 2018 [23]
CHIR99021 Glycogen synthase kinase-3β inhibition Improve the conversion of human fibroblasts to neurons  
DMH1 BMP inhibition Improve the conversion of human fibroblasts to neurons
Repsox Transforming growth factor-β inhibition Improve the conversion of human fibroblasts to neurons
Forskolin ROCK2 inhibition Improve migration of neural crest cells; enable neurogenin 2 to convert human fibroblasts into cholinergic neurons
Y-27632 Rho kinase inhibition Facilitate the maintenance of pluripotent stem cells and neuron survival
SP600125 JNK inhibition Enhance the neuronal conversion of fibroblasts
Neurons CHIR99021 GSK3 inhibition Unknown ASCL1, BRN2, ShREST Unknown Villanueva-Paz et al. 2019 [104]
Noggin BMP inhibition Unknown
Valproic acid HADC inhibition Unknown
SB431542, LDN193189 Unknown A neural fate inducing factor
Dopaminergic neurons CHIR99021, Purmorphamine, Y27632 Unknown Unknown ASCL1, NURR1, LMX1A, miR-124, p53 shRNA Unknown Jiali et al. 2020 [105]