Single-cell analysis of chromatin accessibility in the adult mouse brain.
Songpeng ZuYang Eric LiKangli WangEthan J ArmandSainath MamdeMaria Luisa AmaralYuelai WangAndre ChuYang XieMichael MillerJie XuZhaoning WangKai ZhangBojing JiaXiaomeng HouLin LinQian YangSeoyeon LeeBin LiSamantha KuanHanqing LiuJingtian ZhouAntónio Pinto-DuarteJacinta LuceroJulia OsteenMichael NunnKimberly A SmithBosiljka TasicZizhen YaoHongkui ZengZihan WangJingbo ShangM Margarita BehrensJoseph R EckerAllen WangSebastian PreisslBing RenPublished in: Nature (2023)
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 1-4 . Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated by analysing 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 1,482 distinct brain cell populations, adding over 446,000 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-specifically, 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 the DNA sequence alone. Our results provide a resource for the analysis of cell-type-specific gene regulation programs in both mouse and human brains.
Keyphrases
- single cell
- rna seq
- transcription factor
- high throughput
- white matter
- resting state
- cell therapy
- gene expression
- deep learning
- dna damage
- genome wide
- cerebral ischemia
- public health
- stem cells
- multiple sclerosis
- endothelial cells
- machine learning
- spinal cord
- dna methylation
- functional connectivity
- circulating tumor
- small molecule
- induced apoptosis
- mesenchymal stem cells
- signaling pathway
- brain injury
- cell death
- bone marrow
- blood brain barrier
- genetic diversity