Provided are cortical interneurons and other neuronal cells and
in vitro methods for producing such cortical interneurons and other neuronal cells by the
directed differentiation of stem cells and neuronal
progenitor cells. The present disclosure relates to novel methods of
in vitro differentiation of stem cells and neural
progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic
cholinergic neurons. The present disclose describes the derivation of these cells via inhibiting
SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural
progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic
cholinergic neurons. The present disclosure also relates to compositions of cortical interneurons, hypothalamic neurons or pre-optic
cholinergic neurons, and their precursors, that are highly enriched and can be used in variety of application. These cells can be used therapeutically to treat neurodegenerative and neuropsychiatric disorders, and can be used for
disease modeling and
drug screening.