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A comparative atlas of single-cell chromatin accessibility in the human brain.

Science (New York, N.Y.) | 2023

Recent advances in single-cell transcriptomics have illuminated the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using a single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq), we explored open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveiled 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly a third of the cCREs demonstrated conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer's disease (AD), and major depression, and have developed deep learning models to predict the regulatory roles of noncoding risk variants in these disorders.

Pubmed ID: 37824643 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


BICCN (data or information resource)

RRID:SCR_015820

Consortium for the cell census in the brain. Integrated network of data generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate brains.

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Illumina HiSeq 3000/HiSeq 4000 Sequencing System (portal)

RRID:SCR_016386

Sequencer that uses patterned flow cell technology to provide high-performance sequencing. Perform production-scale, high-throughput exome or transcriptome sequencing projects quickly and economically.

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Illumina NovaSeq 6000 Sequencing System (instrument resource)

RRID:SCR_016387

System unleashes groundbreaking innovations that leverage our proven technology. Now you can get scalable throughput and flexibility for virtually any sequencing method, genome, and scale of project.

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Illumina NextSeq 500 (instrument resource)

RRID:SCR_014983

High-throughput sequencing machine which enables sequencing of exomes, whole genomes, and transcriptomes. It also provides flow cell types, real-time analysis, and integration with Illumina's BaseSpace computing environment.

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Thermo Fisher Qubit fluorimeter (instrument resource)

RRID:SCR_018095

Benchtop fluorometer designed to accurately measure DNA, RNA, and protein quantity. Measures RNA integrity and quality. Touch screen to select and run assays with results displayed in few seconds.

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Beckman Coulter Biomek i7 Hybrid Automated Workstation (instrument resource)

RRID:SCR_018094

Liquid handling instrument designed to optimize dependability and walk-away time. Biomek i7 Hybrid with enclosure has up to 45 deck positions and includes both Multichannel and Span-8 pipette heads in enclosed work space.

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Mettler Toledo BenchSmart 96 (instrument resource)

RRID:SCR_018093

Semi automated pipetting system by Mettler Toledo. Instrument for semi-automated 96/384-well plate pipetting. Semi-Automated 96/384-Well Pipetting System where pipetting options range from 0.5 uL to 1000 uL.

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