A cell atlas of chromatin accessibility across 25 adult human tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE165659 | GEO | 2021/02/16
REPOSITORIES: GEO
Similar Datasets
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.
2021-09-22 | GSE184462 | GEO
Project description:A comparative atlas of single-cell chromatin accessibility in the human brainRecent 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 (ATAC-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.
2023-10-04 | GSE244618 | GEO
Project description:Zebrafish is a popular model for studies of embryonic development. Recent surveys of zebrafish embryogenesis with single-cell transcriptomics have uncovered hundreds of cell types, but the dynamic accessible regions of the genome that determine regulatory programs responsible for the unique identity and function of each cell type during embryogenesis lack detailed study. Here, we present SPATAC-seq: a split-pool ligation-based high-throughput single-cell assay for transposase-accessible chromatin using sequencing. Using SPATAC-seq, we profiled chromatin accessibility in more than 808,046 individual nuclei across 20 developmental stages spanning the sphere stage to the early larval protruding mouth stages in a single experiment. Using this chromatin accessibility map, we identified 604 cell types and inferred their developmental relationships. We also identified 959,040 candidate cis-regulatory elements (cCREs) and delineate development-specific cCREs, as well as transcription factors defining diverse cell identities. Importantly, transient reporter assays confirmed that a majority of tested cCREs exhibited robust enhanced EGFP expression in restricted cell types or tissues. Finally, we explored gene regulatory programs that drive pigment and notochord cell differentiation. Our work provides a comprehensive and valuable open resource for exploring transcriptional regulators that determine cell fate specification in zebrafish embryogenesis.
2024-04-14 | GSE243256 | GEO
Project description:Chromatin accessibility maps of human primary pancreatic cell types
| PRJNA317376 | ENA
Project description:Knowledge of the locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to better understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using multiple epigenetic features in cell types from one species at a time, but such an approach can make it difficult to compare results across species. In contrast, we conducted a cross-species study defining epigenetic states and identifying cCREs in blood cell types to generate maps of the regulatory landscapes and cCREs that are comparable across species. This study used integrative modeling of eight epigenetic features jointly in both human and mouse in our Validated Systematic Integration (VISION) Project. The accuracy of the cCRE predictions was supported by orthogonal function-related data. The contribution of each epigenetic state in cCREs to gene regulation was estimated from a multivariate regression against gene expression across cell types, and these values were used to estimate an epigenetic state Regulatory Potential (esRP) score for each cCRE in each cell type. These esRP scores have broad utility for visualizing and categorizing the dynamic changes in cCREs during hematopoietic differentiation. After jointly clustering cCREs based on their esRP scores across human and mouse cell types, we found distinctive transcription factor binding motifs associated with each group of cCREs with similar patterns of regulatory activity; these associations are similar between human and mouse. Genetic variants associated with blood cell phenotypes (from the GWAS Catalog and the UK Biobank study) were highly and specifically enriched in the catalog of human VISION cCREs, indicating the utility of our cCRE predictions for understanding the impact of noncoding genetic variants on both physiologic and pathologic blood cell-related traits. The cross-species joint modeling enabled a comparison of cCREs that revealed both conserved and lineage-specific patterns of epigenetic evolution, even in the absence of genomic sequence alignment. The VISION project resources are accessible through a suite of tools and browsers at http://usevision.org.
2023-04-10 | GSE229100 | GEO
Project description:Knowledge of the locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to better understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using multiple epigenetic features in cell types from one species at a time, but such an approach can make it difficult to compare results across species. In contrast, we conducted a cross-species study defining epigenetic states and identifying cCREs in blood cell types to generate maps of the regulatory landscapes and cCREs that are comparable across species. This study used integrative modeling of eight epigenetic features jointly in both human and mouse in our Validated Systematic Integration (VISION) Project. The accuracy of the cCRE predictions was supported by orthogonal function-related data. The contribution of each epigenetic state in cCREs to gene regulation was estimated from a multivariate regression against gene expression across cell types, and these values were used to estimate an epigenetic state Regulatory Potential (esRP) score for each cCRE in each cell type. These esRP scores have broad utility for visualizing and categorizing the dynamic changes in cCREs during hematopoietic differentiation. After jointly clustering cCREs based on their esRP scores across human and mouse cell types, we found distinctive transcription factor binding motifs associated with each group of cCREs with similar patterns of regulatory activity; these associations are similar between human and mouse. Genetic variants associated with blood cell phenotypes (from the GWAS Catalog and the UK Biobank study) were highly and specifically enriched in the catalog of human VISION cCREs, indicating the utility of our cCRE predictions for understanding the impact of noncoding genetic variants on both physiologic and pathologic blood cell-related traits. The cross-species joint modeling enabled a comparison of cCREs that revealed both conserved and lineage-specific patterns of epigenetic evolution, even in the absence of genomic sequence alignment. The VISION project resources are accessible through a suite of tools and browsers at http://usevision.org.
2023-04-10 | GSE229099 | GEO
Project description:Knowledge of the locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to better understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using multiple epigenetic features in cell types from one species at a time, but such an approach can make it difficult to compare results across species. In contrast, we conducted a cross-species study defining epigenetic states and identifying cCREs in blood cell types to generate maps of the regulatory landscapes and cCREs that are comparable across species. This study used integrative modeling of eight epigenetic features jointly in both human and mouse in our Validated Systematic Integration (VISION) Project. The accuracy of the cCRE predictions was supported by orthogonal function-related data. The contribution of each epigenetic state in cCREs to gene regulation was estimated from a multivariate regression against gene expression across cell types, and these values were used to estimate an epigenetic state Regulatory Potential (esRP) score for each cCRE in each cell type. These esRP scores have broad utility for visualizing and categorizing the dynamic changes in cCREs during hematopoietic differentiation. After jointly clustering cCREs based on their esRP scores across human and mouse cell types, we found distinctive transcription factor binding motifs associated with each group of cCREs with similar patterns of regulatory activity; these associations are similar between human and mouse. Genetic variants associated with blood cell phenotypes (from the GWAS Catalog and the UK Biobank study) were highly and specifically enriched in the catalog of human VISION cCREs, indicating the utility of our cCRE predictions for understanding the impact of noncoding genetic variants on both physiologic and pathologic blood cell-related traits. The cross-species joint modeling enabled a comparison of cCREs that revealed both conserved and lineage-specific patterns of epigenetic evolution, even in the absence of genomic sequence alignment. The VISION project resources are accessible through a suite of tools and browsers at http://usevision.org.
2023-04-10 | GSE229097 | GEO
Project description:Knowledge of the locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to better understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using multiple epigenetic features in cell types from one species at a time, but such an approach can make it difficult to compare results across species. In contrast, we conducted a cross-species study defining epigenetic states and identifying cCREs in blood cell types to generate maps of the regulatory landscapes and cCREs that are comparable across species. This study used integrative modeling of eight epigenetic features jointly in both human and mouse in our Validated Systematic Integration (VISION) Project. The accuracy of the cCRE predictions was supported by orthogonal function-related data. The contribution of each epigenetic state in cCREs to gene regulation was estimated from a multivariate regression against gene expression across cell types, and these values were used to estimate an epigenetic state Regulatory Potential (esRP) score for each cCRE in each cell type. These esRP scores have broad utility for visualizing and categorizing the dynamic changes in cCREs during hematopoietic differentiation. After jointly clustering cCREs based on their esRP scores across human and mouse cell types, we found distinctive transcription factor binding motifs associated with each group of cCREs with similar patterns of regulatory activity; these associations are similar between human and mouse. Genetic variants associated with blood cell phenotypes (from the GWAS Catalog and the UK Biobank study) were highly and specifically enriched in the catalog of human VISION cCREs, indicating the utility of our cCRE predictions for understanding the impact of noncoding genetic variants on both physiologic and pathologic blood cell-related traits. The cross-species joint modeling enabled a comparison of cCREs that revealed both conserved and lineage-specific patterns of epigenetic evolution, even in the absence of genomic sequence alignment. The VISION project resources are accessible through a suite of tools and browsers at http://usevision.org.
2023-04-10 | GSE229098 | GEO
Project description:Single-Cell Chromatin Accessibility Maps Reveal the Regulatory Programs Driving Early Mouse Organogenesis
| PRJNA550440 | ENA
Project description:Recent surveys of mouse organogenesis cell atlas (MOCA) with single cell transcriptomics have uncovered hundreds of cell types, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each cell type have yet to be elucidated. We applied a four-level combinatorial indexing assay, SPATAC-seq, to profile the chromatin accessibility in >350,000 cells derived from 13 embryos staged between embryonic day (E) 10.5 and 13.5 in a single experiment. The resulting map revealed the status of open chromatin for 844,817 candidate cis-regulatory elements (cCREs) in 33 main cell types and 296 subtypes. By integrating this accessible chromatin atlas with scRNA data of MOCA, we characterized the gene regulatory sequences and transcription factors associated with cell fate commitment, such as unreported role of Nr5a2 and Gata6 in gastrointestinal tract. Finaly, we integrated this atlas with previous scATAC-seq data from mouse embryos at E8.25 and 13 adult mouse tissues to dissect life stage specific gene regulatory programs across different cell types. This rich resource and comprerhensive analysis provide a foundation for expolring gene regulators in mammalian cell differentiation.
2024-04-14 | GSE216371 | GEO