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A human cell atlas of fetal chromatin accessibility

ABSTRACT: A human cell atlas of fetal chromatin accessibility

PROVIDER: PRJNA629599 | ENA |

REPOSITORIES: ENA

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A human cell atlas of fetal chromatin accessibility.

Project description:The chromatin landscape underlying the specification of human cell types is of fundamental interest. We generated human cell atlases of chromatin accessibility and gene expression in fetal tissues. For chromatin accessibility, we devised a three-level combinatorial indexing assay and applied it to 53 samples representing 15 organs, profiling ~800,000 single cells. We leveraged cell types defined by gene expression to annotate these data and cataloged hundreds of thousands of candidate regulatory elements that exhibit cell type-specific chromatin accessibility. We investigated the properties of lineage-specific transcription factors (such as POU2F1 in neurons), organ-specific specializations of broadly distributed cell types (such as blood and endothelial), and cell type-specific enrichments of complex trait heritability. These data represent a rich resource for the exploration of in vivo human gene regulation in diverse tissues and cell types.

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A human cell atlas of fetal chromatin accessibility

Project description:We devised an improved assay for single cell profiling of chromatin accessibility with three-level combinatorial indexing (sci-ATAC-seq3). We applied this method to 53 fetal tissue samples representing 15 organs, altogether profiling approximately one million single cells. We leveraged cell types defined by gene expression in the same organs to annotate these data, and built a catalog of hundreds-of-thousands of candidate gene regulatory elements exhibiting cell type-specific accessibility. Our analyses focus on the properties of lineage-specific transcription factors, organ-specific specializations of broadly distributed cell types, and cell type-specific enrichments of complex trait heritability. Additional data formats are available at atlas.brotmanbaty.org.

2020-11-01 | GSE149683 | GEO

A cell atlas of chromatin accessibility across 25 adult human tissues

Project description:Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile the activity of human gene regulatory elements in diverse cell types and tissues in the human body, we applied single cell chromatin accessibility assays to 25 distinct human tissue types from multiple donors. The resulting chromatin maps comprising ~500,000 nuclei revealed the status of open chromatin for over 750,000 candidate cis-regulatory elements (cCREs) in 54 distinct cell types. We further delineated cell type-specific and tissue-context dependent gene regulatory programs, and developmental stage specificity by comparing with a recent human fetal chromatin accessibility atlas. We finally used these chromatin maps to 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 and organ systems.

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

Project description: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 single-cell chromatin accessibility data from 15 fetal tissue types to reveal the status of open chromatin for approximately 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.

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