A single-cell atlas of chromatin accessibility in the human genome

Kai Zhang; James D Hocker; Michael Miller; Xiaomeng Hou; Joshua Chiou; Olivier B Poirion; Yunjiang Qiu; Yang E Li; Kyle J Gaulton; Allen Wang; Sebastian Preissl; Bing Ren

doi:10.1016/j.cell.2021.10.024

A single-cell atlas of chromatin accessibility in the human genome

Cell. 2021 Nov 24;184(24):5985-6001.e19. doi: 10.1016/j.cell.2021.10.024. Epub 2021 Nov 12.

Authors

Affiliations

¹ Ludwig Institute for Cancer Research, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
² Ludwig Institute for Cancer Research, La Jolla, CA, USA; Medical Scientist Training Program, University of California San Diego, La Jolla, CA, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA.
³ Center for Epigenomics, University of California San Diego, La Jolla, CA, USA.
⁴ Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA; Department of Pediatrics, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA, USA.
⁵ Ludwig Institute for Cancer Research, La Jolla, CA, USA.
⁶ Department of Pediatrics, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
⁷ Ludwig Institute for Cancer Research, La Jolla, CA, USA; Center for Epigenomics, University of California San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA. Electronic address: biren@health.ucsd.edu.

Abstract

Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile the activity of gene regulatory elements in diverse cell types and tissues in the human body, we applied single-cell chromatin accessibility assays to 30 adult human tissue types from multiple donors. We integrated these datasets with previous single-cell chromatin accessibility data from 15 fetal tissue types to reveal the status of open chromatin for ∼1.2 million candidate cis-regulatory elements (cCREs) in 222 distinct cell types comprised of >1.3 million nuclei. We used these chromatin accessibility maps to delineate cell-type-specificity of fetal and adult human cCREs and to systematically interpret the noncoding variants associated with complex human traits and diseases. This rich resource provides a foundation for the analysis of gene regulatory programs in human cell types across tissues, life stages, and organ systems.

Keywords: GWAS; chromatin accessibility; cis regulatory elements; enhancers; epigenome; noncoding variants; single cell ATAC-seq.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Chromatin / metabolism*
Cluster Analysis
Fetus / metabolism
Genetic Variation
Genome, Human*
Genome-Wide Association Study
Humans
Organ Specificity
Phylogeny
Regulatory Sequences, Nucleic Acid / genetics
Risk Factors
Single-Cell Analysis*

Substances

Chromatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding