A comparative atlas of single-cell chromatin accessibility in the human brain
Сравнительный атлас доступности хроматина на одиночных клетках человеческого мозга
2023-10-12
SCID: 54.1/3pj4rg7h
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candidate cis-regulatory elements (cCREs)cell-type specific regulatory landscapesneuropsychiatric disorder risk variant predictionsingle-cell chromatin accessibilitysingle-nucleus ATAC-seq
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Abstract (AI)
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.
Key Findings
1
Approximately one third of the identified cCREs are conserved and show chromatin accessibility in corresponding mouse brain cell types.
2
Developed deep learning models to predict regulatory effects of noncoding risk variants relevant to these neuropsychiatric disorders.
3
Found strong associations between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer’s disease, and major depression.
4
Generated snATAC-seq profiles of chromatin accessibility across 1.1 million nuclei from 42 human brain regions across three adults.
5
Identified 107 distinct cell types and mapped usage of 544,735 candidate cis-regulatory DNA elements (cCREs) across those cell types.
Research Object
Single-cell chromatin accessibility atlas of human brain nuclei (snATAC-seq profiles across 1.1 million nuclei from 42 brain regions)
Research Subject
Cell-type-resolved open chromatin landscapes and usage of candidate cis-regulatory elements across human brain cell types, and their links to neuropsychiatric disease-associated noncoding variants
Publication Details
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2023-10-12
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