Single cell atlas of the human optic nerve

The optic nerve is essential for transmitting visual information from the retina to the brain, where it is processed into images. Damage to the optic nerve can cause vision loss, leading to conditions such as glaucoma, optic neuritis, and optic neuropathy. To advance our understanding of the transcriptomic and epigenetic landscapes, as well as the dynamic cellular processes of the optic nerve, we conducted single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) on the optic nerve head (ONH) and optic nerve (ON) tissues from over 80 healthy human donor eyes spanning diverse ages, genders, and ethnic backgrounds. By integrating newly generated and previously published snRNA-seq datasets, we constructed a comprehensive ONH and ON cell atlas encompassing transcriptomic profiles of 959,629 nuclei. Our analysis identified 25 distinct cell classes and 86 cell types/states, including diverse populations of astrocytes, oligodendrocytes, oligodendrocyte precursor cells, microglia, and macrophages. Furthermore, snATAC-seq profiling of approximately 1 million nuclei generated high-resolution chromatin accessibility landscapes, enabling the identification of cis-regulatory elements and transcription factors specific to individual cell classes and types. As part of the Human Cell Atlas initiative, our ON atlas serves as a crucial resource for studying optic nerve physiology and deepening our understanding of the cellular and molecular mechanisms underlying optic neuropathies and related diseases.