Accelerated High-Yield Generation of Limb-Innervating Motor Neurons from Human Stem Cells

摘要: Human pluripotent stem cells are a promising source of differentiated for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even intensely studied types like spinal motor neurons is hindered by the long duration low yields existing protocols in vitro differentiation molecular heterogeneity populations generated. We report combination small molecules that within 3 weeks induce at up to 50% abundance with defined subtype identities relevance neurodegenerative disease. Despite accelerated differentiation, expressed combinations HB9, ISL1, column-specific markers mirror those observed vivo human embryonic cord. They also exhibited spontaneous induced activity, projected axons toward muscles when grafted into developing chick Strikingly, this novel protocol preferentially generates expressing limb-innervating lateral column (FOXP1(+)/LHX3(-)). Access high-yield cultures neuron subtypes will facilitate in-depth study subtype-specific properties, development large-scale cell-based screening assays.