Review Article

Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

Table 1


Cell typeStudyCulture methodProgramme of developmental cues for neural conversion and patterningDuration (days)

Cortical precursorsWatanabe et al. 2007 [44]Serum-free embryoid body-like (SFEB)BMP antagonist (BMPRIA-Fc)
Activin/Nodal antagonist (LeftyA)
Wnt antagonist (Dkk1)
35

Cortical neuronsEiraku et al. 2008 [45]SFEB derivativeBMP antagonist (BMPRIA-Fc)
Activin/Nodal antagonist (LeftyA)
Wnt antagonist (Dkk1)
45–60

Cortical neuronsChambers et al. 2009 [16]MonolayerBMP antagonist (NOGGIN)
Activin/Nodal antagonist (SB431542)
19

Cortical neurons and MGE/LGE neuronsLi et al. 2009 [47]Suspension None for cortical (endogenous Wnt)
For MGE and LGE derivatives:
Wnt antagonist (Dkk1)
Sonic hedgehog (SHH)
30–35

Cortical neuronsShi et al. 2012 [46]MonolayerBMP antagonist (NOGGIN)
Activin/Nodal antagonist (SB431542)
80–100

Midbrain dopaminergic neurons Kriks et al. 2011 [50]MonolayerBMP antagonist (NOGGIN or LDN)
Activin/Nodal antagonist (SB431542)
Sonic hedgehog (SHH and purmorphamine),
Fibroblast Growth Factor 8b (FGF8b),
Wnt agonist (CHIR99021)
80

Midbrain dopaminergic neuronsKirkeby et al. 2012 [48]Embryoid body BMP antagonist (NOGGIN)
Activin/Nodal antagonist (SB431542)
Wnt agonist (CT99021)
Sonic hedgehog (SHH-C24II)
35

Midbrain dopaminergic neuronsJaeger et al. 2011 [52]MonolayerBMP antagonist (NOGGIN)
Activin/Nodal antagonist (SB431542)
FGF/ERK antagonist (PD0325901)
Fibroblast Growth Factor 8b (FGF8b),
Sonic hedgehog (SHH)
30–35

Cerebellar neuronsErceg et al. 2012 [59]Embryoid bodyFibroblast Growth Factors (FGF8, FGF4, and FGF2)
Retinoic acid (RA)
Wnt agonists (Wnt1, Wnt3a)
BMPs (BMP4, BMP6, BMP7, and GDF7)
Sonic hedgehog (SHH)
35

Cerebellar neuronsMuguruma et al. 2015 [57]SFEBqActivin/Nodal antagonist (SB431542)
Fibroblast Growth Factors (FGF2, FGF19)
Insulin
Stromal cell-derived factor 1 (SDF-1)
(co-culture with mouse granule cells to generate Purkinje cells)
35–135

Cerebellar neuronsWang et al. 2015 [58]Embryoid bodyFibroblast growth factor (FGF2)
Insulin
Sonic hedgehog antagonist (cyclopamine)
(coculture with rat organotypic cerebellar slice to generate Purkinje cells)
20–65

Spinal cord motor neuronsLi et al. 2005 [63]MonolayerRetinoic acid (RA)
Sonic hedgehog (SHH)
Fibroblast Growth Factor (FGF2)
21–35

Spinal cord motor neuronsPatani et al. 2011 [18]SuspensionActivin/Nodal antagonist (SB431542)
Sonic hedgehog (purmorphamine)
Fibroblast Growth Factor (FGF2)
21–35

Spinal cord motor neuronsCalder et al. 2015 [67]MonolayerActivin/Nodal antagonist (SB431542)
BMP antagonist (LDN193189)
Retinoic acid (RA)
35–40