A distinct lineage pathway drives parvalbumin chandelier cell fate in human interneuron reprogramming.

ABSTRACT: Direct lineage reprogramming of glial cells to induced neurons has the potential for restoring brain circuits and function in neuronal disorders and states. We introduce three-dimensional (3D) human glia reprogramming into neurons with a GABAergic interneuron phenotype using stem cell-derived human glia. Single-nucleus RNA sequencing of the converted cells demonstrates distinct neuronal clusters within 2 weeks, including a parvalbumin (PV) cluster with high neuronal maturity and features of chandelier interneurons. A lineage trajectory analysis of the glia-to-neuron conversion reveals a distinct lineage pathway to PV chandelier fate, including various neuronal developmental stages and the establishment of synaptic machinery. This analysis reveals PV fate-important genes that are previously

SUBMITTER: Stamouli CA 

PROVIDER: S-EPMC12757047 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature