Single-cell 3D Genome and Multiome of the Human and Mouse Cerebellum

The cerebellum contains most of the neurons in the human brain and exhibits distinctive modes of development and aging. In this work, by developing our single-cell three-dimensional (3D) genome assay—diploid chromosome conformation capture, or Dip-C—into population-scale (Pop-C) and virus-enriched (vDip-C) modes, we resolved the first 3D genome structures of single cerebellar cells, created life-spanning 3D genome atlases for both humans and mice, and jointly measured transcriptome and chromatin accessibility during development. We found that although the transcriptome and chromatin accessibility of cerebellar granule neurons mature in early postnatal life, 3D genome architecture gradually remodels throughout life, establishing ultra–long-range intrachromosomal contacts and specific interchromosomal contacts that are rarely seen in neurons. These results reveal unexpected evolutionarily conserved molecular processes that underlie distinctive features of neural development and aging across the mammalian life span. In this project, we have performed single-cell Dip-C, RNA-seq, and ATAC-seq on human and mouse cerebellum tissues. Please note that the original 12,004 samples are collapsed to represent as 42 sample records. The original 12,004 sample annotations are provided in the Series 'README_sample_annotations.txt' supplementary file, including the associated raw and processed data file information.