TABLE 2.
Small molecules, inhibitor, transcription factors, and growth factors used for iPSC, ECS, and NPC differentiation and transdifferentiation.
| Substance/Factor | Function | Differentiation step | References |
| TGF-β RI kinase inhibitor VI (SB-431542) |
- BMP/TGF-β signaling inhibition - Enhanced neuronal differentiation - Induction of ventral telencephalic specification - PSC differentiation into neuroepithelial cells |
Neural induction | Delli Carri et al., 2013; Nicoleau et al., 2013; Arber et al., 2015; Adil et al., 2018; Comella-Bolla et al., 2020; Grigor’eva et al., 2020; Vigont et al., 2021 |
| Patterning | Delli Carri et al., 2013 | ||
| Noggin | - BMP/TGF-β signaling inhibition - PSC differentiation into neuroepithelial cells |
Neural induction and patterning | Delli Carri et al., 2013; Nicoleau et al., 2013; Nekrasov et al., 2016 |
| Purmorphamine | - BMP signaling inhibition - Enhanced neuronal differentiation |
Neural induction | El-Akabawy et al., 2011; Adil et al., 2018 |
| Patterning | El-Akabawy et al., 2011; Nekrasov et al., 2016; Adil et al., 2018; Grigor’eva et al., 2020; Vigont et al., 2021 | ||
| Maturation | El-Akabawy et al., 2011 | ||
| Brain-derived neurotrophic factor | - Neuronal survival factor - Increase the proportion of DARP-32-positive neurons |
Patterning | Zhang et al., 2010; Delli Carri et al., 2013; Lin et al., 2015; Adil et al., 2018; Grigor’eva et al., 2020 |
| Maturation | El-Akabawy et al., 2011; Delli Carri et al., 2013; Nicoleau et al., 2013; Victor et al., 2014; Arber et al., 2015; Lin et al., 2015; Nekrasov et al., 2016; Wu M. et al., 2018; Comella-Bolla et al., 2020; Grigor’eva et al., 2020; Vigont et al., 2021 | ||
| Dihydrochloride (LDN-193189) | - BMP/TGF-β signaling inhibition - Induction of ventral telencephalic specification |
Neural induction | Arber et al., 2015; Wu M. et al., 2018; Comella-Bolla et al., 2020; Grigor’eva et al., 2020; Vigont et al., 2021 |
| Sonic hedgehog | - Induction of forebrain neurogenesis - Promote differentiation into DARPP-32-positive neurons |
Patterning | Zhang et al., 2010; El-Akabawy et al., 2011; Delli Carri et al., 2013; Nicoleau et al., 2013; Lin et al., 2015 |
| Basic fibroblast growth factor | - Neuronal survival factor | Neural induction | Al-Gharaibeh et al., 2017 |
| Patterning | Zhang et al., 2010; Nekrasov et al., 2016; Grigor’eva et al., 2020; Vigont et al., 2021 | ||
| Glial cell line-derived neurotrophic factor | - Neuronal survival factor | Maturation | Arber et al., 2015; Lin et al., 2015; Adil et al., 2018; Wu M. et al., 2018; Vigont et al., 2021 |
| Dorsomorphin | - BMP signaling inhibition - Enhanced neuronal differentiation - Induction of ventral telencephalic specification - PSC differentiation into neuroepithelial cells |
Neural induction | Arber et al., 2015; Nekrasov et al., 2016; Grigor’eva et al., 2020 |
| Forskolin | - cAMP pathway activator | Patterning and maturation |
Nekrasov et al., 2016 |
| Maturation | Comella-Bolla et al., 2020; Vigont et al., 2021 | ||
| Activin A | - TGF-β/BMP signaling pathway activation - Induction of forebrain neurogenesis - Differentiation in the lateral ganglionic eminence - Promote differentiation into DARPP-32-positive neurons |
Patterning and maturation | Arber et al., 2015; Grigor’eva et al., 2020 |
| Dibutyryl-cAMP | - Cell-permeable analog of cAMP - Enhance the output of depolarized neurons - Stimulate GABAergic MSNs neurogenesis |
Maturation | Zhang et al., 2010; El-Akabawy et al., 2011; Nicoleau et al., 2013; Victor et al., 2014; Lin et al., 2015; Adil et al., 2018; Grigor’eva et al., 2020 |
| Ascorbic acid |
- Formation and maintenance of the neural microenvironment - Neuroprotective |
Maturation | Wu M. et al., 2018; Comella-Bolla et al., 2020; Grigor’eva et al., 2020 |
| ROCK inhibitor (Y-27632) |
- Stem cell survival factor | Neural induction | Compagnucci et al., 2016; Comella-Bolla et al., 2020 |
| Patterning | Zhang et al., 2010; Delli Carri et al., 2013; Lin et al., 2015; Compagnucci et al., 2016; Grigor’eva et al., 2020 | ||
| Valproic acid; Valpromide | - Stimulation of GABAergic MSN neurogenesis | Maturation | Zhang et al., 2010; El-Akabawy et al., 2011; Nicoleau et al., 2013; Victor et al., 2014 |
| Neurotrophin-3 | - Neurotrophic factor | Maturation | Victor et al., 2014 |
| Retinoid acid | - Induce GABAergic differentiation | Patterning and maturation | El-Akabawy et al., 2011; Victor et al., 2014 |
| WNT inhibitor dickkopf 1 | - WNT signaling inhibition | Patterning | Zhang et al., 2010; El-Akabawy et al., 2011; Delli Carri et al., 2013; Nicoleau et al., 2013; Adil et al., 2018 |
| Insulin | - Proliferation improvement | Patterning | Delli Carri et al., 2013; Shahbazi et al., 2019 |
| Maturation | Delli Carri et al., 2013; Lin et al., 2015; Shahbazi et al., 2019 | ||
| Insulin-like growth factor 1 | - Synapse formation | Maturation | Lin et al., 2015; Nieto-Estévez et al., 2016; Adil et al., 2018 |
| Tankyrase inhibitor (IWR1) | - WNT signaling inhibition | Neural induction and patterning | Comella-Bolla et al., 2020 |
| Tankyrase inhibitor (XAV-939) |
- WNT signaling inhibition | Patterning | Wu M. et al., 2018 |