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AssigneesMemorial Sloan Kettering Cancer Center, Cornell University
InventorsLorenz Studer, Asif M. Maroof, Stewart Anderson
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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 disclosure 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.
An in vitro method for generating neurons through differentiation of human pluripotent or multipotent cells, said neurons comprising one or more markers indicating a preoptic cholinergic neuron, a pre-optic cholinergic neuron precursor, a cortical interneuron, a cortical interneuron precursor, a hypothalamic neuron or a hypothalamic neuron precursor, the method comprising:
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