PhD Candidate Leiden University Leiden, Netherlands
Abstract: The dorsal root ganglia (DRG) relays somatosensory information and play a critical role in disorders, such as neuropathic pain, however ex vivo models for the DRG have not yet been established. Peripheral sensory neurons, Schwann cell, and satellite glia (SG) that make up the DRGs, originate from neuromesodermal progenitors (NMPs) giving rise progressively to neural crest progenitors in the formation of 31 pairs of DRGs in the human embryo axis. We derived human axial stem cells (AxSCs) that emulate NMPs from iPS cells and leveraged them to develop novel differentiation protocols for the DRG cells. We found that manipulating Notch signalling governs the bifurcation of sensory- and autonomic-peripheral neurons versus Schwann cells and SG. Moreover, co-culturing these populations improves glial cell maturation markers (e.g. PLP1, MPZ, FABP7), captures nerve-associated glial cell migration, and increases myelination. AxSCs enable faster, more homogeneous differentiation than PSCs, offering a scalable system to model trilineage interactions in the DRG.
