The paper details a comprehensive study that generated a candidate cis-regulatory DNA element (cCRE) atlas of the adult mouse brain through single-cell analysis of chromatin accessibility in over 2.3 million cells. Researchers used single-nucleus assay for transposase-accessible chromatin followed by sequencing (snATAC-seq) across 117 anatomical dissections to identify approximately 1 million cCREs and delineate 1,482 distinct brain cell populations. The work integrated this data with single-cell RNA sequencing to infer gene regulatory networks (GRNs) in over 260 subclasses of brain cells, noting that many mouse-specific cCREs are enriched for transposable elements (TEs), suggesting a role in neuronal diversity. Finally, the study developed deep-learning models capable of accurately predicting chromatin accessibility from DNA sequence alone, even successfully translating the predictive capacity to matched human brain cell types. This resource significantly expands the understanding of cell-type-specific gene regulation in the mammalian brain.
References:
- Zu S, Li Y E, Wang K, et al. Single-cell analysis of chromatin accessibility in the adult mouse brain[J]. Nature, 2023, 624(7991): 378-389.