학술논문

Single-cell analysis of chromatin accessibility in the adult mouse brain
Document Type
article
Source
Nature. 624(7991)
Subject
Biochemistry and Cell Biology
Bioinformatics and Computational Biology
Genetics
Biological Sciences
Stem Cell Research
Neurosciences
Biotechnology
Underpinning research
1.1 Normal biological development and functioning
Neurological
Animals
Humans
Mice
Brain
Cerebral Cortex
Chromatin
Deep Learning
DNA Transposable Elements
Gene Regulatory Networks
Neurons
Single-Cell Analysis
General Science & Technology
Language
Abstract
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 complete1-4. 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.