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 | Â | Â | ||
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 | Â | ||||
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] |