Fig. 3: Neurodevelopmental principle for neural lineage subtype specification that guide the directional differentiation of NSCs from different sources in vitro.

A Morphogen gradients, including BMP, WNT, FGF, SHH and RA, define transcription codes of various neural lineage subtypes in corresponding brain regions during early neural development both along the rostral-caudal and dorsal-ventral axes. The depicted neural lineage subtypes include the MSN in ventral TEL, the cortical glutaminergic neuron in dorsal TEL, the DAergic in ventral MES, the motor neuron in spinal cord, the OPC in forebrain and spinal cord. B By using the same chemical or TF patterning principles as seen in vivo, NSCs from different sources can be directional differentiated towards neural lineage subtypes in vitro. The methods of inducing differentiation of NSCs in vitro mainly include external chemical defined system and TF-mediated system. Changes in culture environment include two-dimensional and three-dimensional culture. Overexpression of TFs through viral transduction or non-viral mediated transfection, such as electroporation. BMP bone morphogenic protein, DI diencephalon, FGF fibroblast growth factor, MES mesencephalon, MET metencephalon, MSN medium spiny γ-aminobutyric acid–mediated neurons, MYE myelencephalon, NSC neural stem cell, OPC oligodendrocyte precursor cell, RA retinoic acid, SHH sonic hedgehog, TEL telencephalon, TF transcription factor, WNT wingless-type MMTV integration site family, 2D two-dimensional, 3D three-dimensional.