Human pluripotent stem cells (hES/hiPSC) are able to generate many different cells types of the body and hold substantial potential to study human development and disease in vitro. We direct neuronal development of hES/hiPSC into specific neuronal subtypes of projections neurons to better understand what factors control neuronal diversity in the developing human cortex. Our long term goal is to apply this knowledge to generate distinct projection neuron subtypes. Of particular interest to us are corticospinal motor neurons (CSMN) the neuronal subtype primarily affected in amyotrophic lateral sclerosis (ALS). Generating these clinically relevant neurons holds substantial potential for mechanistic modelling, therapeutic screening and potentially cell replacement therapeutic use, such as corticospinal circuit regeneration and additionally enables investigation of mechanisms underlying ALS pathology in the cerebral cortex.

Selected Publications:

• Sances, S. et al. Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nat Neurosci 19, 542–553 (2016). Pubmed
• Sadegh, C. & Macklis, J. D. Established monolayer differentiation of mouse embryonic stem cells generates heterogeneous neocortical-like neurons stalled at a stage equivalent to midcorticogenesis. J Comp Neurol 522, 2691–2706 (2014). Pubmed