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AssigneeMemorial Sloan Kettering Cancer Center
InventorsLorenz Studer, Stuart M. Chambers, Yuchen Qi, Yvonne Marissa Mica
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The present invention relates to the field of stem cell biology, in particular the linage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC), human induced pluripotent stem cells (hiPSC), somatic stem cells, cancer stem cells, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC to nociceptors (i.e. nociceptor cells) using novel culture conditions. The nociceptors made using the methods of the present invention are further contemplated for various uses including, but limited to, use in in vitro drug discovery assays, pain research, and as a therapeutic to reverse disease of, or damage to, the peripheral nervous system (PNS). Further, compositions and methods are provided for producing melanocytes from human pluripotent stem cells for use in disease modeling.
A kit comprising a first signaling inhibitor, a second signaling inhibitor and a third signaling inhibitor, wherein said first inhibitor is capable of lowering transforming growth factor beta (TGFβ)/Activin-Nodal signaling, said second inhibitor is capable of lowering Small Mothers Against Decapentaplegic (SMAD) signaling and said third inhibitor is capable of lowering glycogen synthase kinase 3β (GSK3β) for activation of wingless (Wnt) signaling, further comprising instructions for inducing directed differentiation of a pluripotent stem cell into a differentiated neural crest lineage cell or a neuronal lineage cell, in vitro, comprising (i) contacting said stem cell with said first and said second inhibitors for up to 96 hours and (ii) contacting said stem cell with said third inhibitor for up to 240 hours.
A kit comprising a first signaling inhibitor, a second signaling inhibitor, and a third signaling inhibitor, wherein said first inhibitor is capable of lowering transforming growth factor beta (TGFβ)/Activin-Nodal signaling, said second inhibitor is capable of lowering Small Mothers Against Decapentaplegic (SMAD) signaling, and said third inhibitor is capable of lowering glycogen synthase kinase 3β (GSK3β) for activation of wingless (Wnt) signaling, further comprising a fourth inhibitor that lowers fibroblast growth factor (FGF) receptor family signaling, wherein said FGF receptor family signaling comprising vascular endothelial growth factor (VEGF) receptor signaling, fibroblast growth factor (FGF) receptor signaling, and platelet-derived growth factor (PDGF) tyrosine kinase receptor signaling.
A kit comprising a first signaling inhibitor, a second signaling inhibitor and a third signaling inhibitor, wherein said first inhibitor is capable of lowering transforming growth factor beta (TGFβ)/Activin-Nodal signaling, said second inhibitor is capable of lowering Small Mothers Against Decapentaplegic (SMAD) signaling and said third inhibitor is capable of lowering glycogen synthase kinase 3β (GSK3β) for activation of wingless (Wnt) signaling, further comprising an inhibitor capable of lowering Notch signaling.
A method for inducing directed differentiation of a pluripotent stem cell, comprising
A method of screening a biological agent in vitro, comprising,
Dependencies are inferred from the claim text.