Comprehensive single-cell analysis of chromatin accessibility in the adult mouse brain

"The tens of millions of neurons and non-neuronal cells in the mouse brain are organized into numerous circuits and structures to carry out complex behaviors and neurological functions. Recent advances in single-cell technologies have led to the discovery of thousands of brain cell types, however, our understanding of the gene regulatory programs in these cell types is far from complete. Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated through examination of the chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1482 distinct brain cell populations, adding over 446,000 new cCREs to the most recent such annotation in the mouse genome. The mouse brain cCREs are moderately conserved in the human brain. The mouse specific cCREs, in particular those identified from a subset of cortical excitatory neurons, are strongly enriched for transposable elements, suggesting a potential role for transposable elements in the emergence of new regulatory programs and neuronal diversity. Finally, we infer the gene regulatory networks in over 260 subclasses of mouse brain cells, and develop deep learning models to predict the activities of gene regulatory elements in different brain cell types from DNA sequence alone. Our results provide a resource for analysis of cell-type-specific gene regulation programs in both mouse and human brains."

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