Modular derivation of diverse, regionally discrete human posterior CNS neurons enables discovery of transcriptomic patterns.

Our inability to derive the neuronal diversity that comprises the posterior central nervous system (pCNS) using human pluripotent stem cells (hPSCs) poses an impediment to understanding human neurodevelopment and disease in the hindbrain and spinal cord. Here, we establish a modular, monolayer differentiation paradigm that recapitulates both rostrocaudal (R/C) and dorsoventral (D/V) patterning, enabling derivation of diverse pCNS neurons with discrete regional specificity. First, neuromesodermal progenitors (NMPs) with discrete profiles are converted to pCNS progenitors (pCNSPs).