Generation of Cholinergic and Dopaminergic Interneurons from Human Pluripotent Stem Cells as a Relevant Tool for In Vitro Modeling of Neurological Disorders Pathology and Therapy

Figure 2

Comparison of different protocols for deriving of basal forebrain cholinergic neurons from hESCs and hiPSCs. (a) Generation of BFCNs from neurospheres through neural progenitor cell stage. Predominantly pure population of basal forebrain cholinergic neurons (BFCNs) was derived from hPSCs by using diffusible ligands presented in the forebrain during a development [12]. Pretreatment with SHH and FGF8 was used to differentiate hPSCs towards a forebrain progenitor fate [12]. Treatment with NGF promoted the differentiation into functionally mature BFCNs [12, 13]. (b) Direct generation of BFCNs from cells growing in neurospheres. Neural development was induced in neurosphere-based nonadherent differentiation in presence of mitogens and ROCK inhibitor Y27632 [14]. Neurospheres derived from hPSCs exposed to neurotrophins, BDNF, CNTF, NT-4, and NGF, increased neuronal differentiation and cholinergic phenotype specification [15]. Composition of the basic medium can be different within the above protocols.

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