PEDIA-BRAIN: A single nuclei multiomic encyclopedia of the human pons provides a resource for normal development and disease vulnerability

Abstract The human pons relays information between the brain and the body. It is affected by pathological processes, including diffuse midline gliomas (DMGs) and multiple sclerosis (MS) which predominantly arise in childhood and middle age, respectively. Although multiple studies address these disease states, a comprehensive resource for normal pons development is lacking. Here we present the first installment of PEDIA-BRAIN, an encyclopedia of gene expression and chromatin accessibility from 140,771 human pons nuclei spanning the first trimester to early adulthood, as a resource for the scientific community. Exploration of the encyclopedia identified two trajectories to mature oligodendrocytes and developmental restriction of genes for neuron to oligodendrocyte progenitor cell synapses. To illustrate the utility of the resource, we compared single cell transcriptomes from DMG and MS tissues to the encyclopedia and identified perturbation of oligodendrocyte subtypes in both diseases. Data may be accessed at https://pediabrain.nchgenomics.org. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵* Lead contact: Michelle A. Wedemeyer, MD/PhD, 700 Children’s Dr, Columbus, OH 43205 Addition of transcription factor motif and footprinting analysis, immuhistochemical validation, and use of pseudbulking with DESe2 for differential gene/peak teasting.