Neural lineage differentiation of human pluripotent stem cells: Advances in disease modeling

Table 1 Comparison of methods for neural induction from human pluripotent stem cells

Method	Neural induction outcomes	Significance	Ref.
Embryoid bodies; selected neural rosettes; 2D and 3D culture	Neural tube-like rosettes stained with Nestin, Musashi-1 and NCAM; positive neuronal markers MAP2 and TUJ1 expression	First study of neural progenitor differentiation from hPSCs	Zhang et al[22], 2001
SFEBq aggregate; sorting cells; 3D culture	Self-organized structure with four distinct zones: ventricular, early and late cortical-plate, and Cajal-Retzius cell zones	Pure 3D culture, provides the basis for the brain organoid method	Eiraku et al[23], 2008
Dual SMAD inhibition; 2D monolayer culture	Complete neural conversion of > 80% of hESCs	Mostly wild used method; also enables neural induction in 3D culture	Chambers et al[24], 2009
Dual SMAD inhibition combined with retinoid signaling; 2D monolayer culture	More than 95% of hPSCs were PAX6 and OTX1/2 cortical progenitor cells in 15 d	Improved the dual SMAD inhibition protocol and higher neural induction efficiency	Shi et al[62], 2012
Cortical organoid/spheroid; 3D culture	Form layered structure tissues partially mimicking human cerebral cortex	Mostly brain-like tissue with some functions	Lancaster et al[17], 2013; Paşca et al[26], 2015; Qian et al[27], 2016
Dual SMAD inhibition combined with Wnt, FGF and Notch inhibition	Generate functional cortical neuron in 16 d	Improved the dual SMAD inhibition protocol and accelerated neural induction	Qi et al[28]

EB: Embryoid body; FGF: Fibroblast growth factor; hPSCs: Human pluripotent stem cells; MAP2: Microtubule-associated protein 2; NCAM: Neural cell adhesion molecule; OTX: Orthodenticle homeobox; PAX6: Paired box 6; SFEBq: Serum-free floating culture of EB-like aggregates with quick aggregation.