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

Ding, T.; Schweickart, G.; Rivaldi, A.; Harrington, C.; Varghese, A.; Qin, K.; Kelly, B. K.; Lammi, G.; Sunkel, B. D.; Stahl, K. L.; Wagner, A. H.; Leonard, J. R.; Isaacs, A. M.; Mardis, E. R.; Miller, K. E.; Wedemeyer, M. A.

doi:10.1101/2025.09.21.677597

bioRxiv · 10.1101/2025.09.21.677597

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

Ding, T.·Schweickart, G.·Rivaldi, A.·Harrington, C.·Varghese, A.·Qin, K.·Kelly, B. K.·Lammi, G.·Sunkel, B. D.·Stahl, K. L.·Wagner, A. H.·Leonard, J. R.·Isaacs, A. M.·Mardis, E. R.·Miller, K. E.·Wedemeyer, M. A.

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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.

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Ding, T., Schweickart, G., Rivaldi, A., Harrington, C., Varghese, A., Qin, K., Kelly, B. K., Lammi, G., Sunkel, B. D., Stahl, K. L., Wagner, A. H., Leonard, J. R., Isaacs, A. M., Mardis, E. R., Miller, K. E., Wedemeyer, M. A.. 2025-09-21. PEDIA-BRAIN: A single nuclei multiomic encyclopedia of the human pons provides a resource for normal development and disease vulnerability. https://doi.org/10.1101/2025.09.21.677597

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