Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrative single-cell chromatin and transcriptome profiling uncovers cell-type specific regulatory interactions

ABSTRACT: Simultaneous measurement of different molecular aspects of gene regulation can help infer functional relationships between genome regulation and gene expression, and understand their distinct and contribution to cell phenotype. Here, we present SHARE-seq, a highly scalable, sensitive, and cost-effective approach for joint measurement of chromatin accessibility and gene expression from the same single cells. Applying SHARE-seq to adult mouse tissues (skin, brain, lung) we show a direct congruence in cell type definition by either chromatin accessibility or RNA expression and create cell-type specific regulatory maps. We leverage naturally occurring cell-cell variation to infer chromatin-expression regulatory relationships and develop a broadly applicable computational strategy to define cis- ad trans- regulatory programs. The cis-regulatory programs, which largely overlap with super-enhancers, are found at key lineage-specifying genes. We demonstrate dynamic chromatin evidence of both gene expression lineage-priming and lineage-memory. The combined scalability and depth of SHARE-seq provide an extensible platform to study the regulatory relationships governing chromatin and gene expression changes across diverse cells within tissues.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE140203 | GEO | 2020/10/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Integrative analysis of haplotype-resolved epigenomes across human tissues

Project description:Allelic differences between the two sets of chromosomes can affect the propensity of inheritance in humans, but the extent of such differences in the human genome has yet to be fully explored. Here, we delineate allelic chromatin modifications and transcriptomes amongst a broad set of human tissues, enabled by a chromosome-span haplotype reconstruction strategy1. The resulting haplotype-resolved epigenomic maps reveal extensive allele bias in the transcription of human genes as well as chromatin state, allowing us to infer cis-regulatory relationships between genes and their control sequences. These maps also uncover a new class of cis regulatory elements and detail activities of repetitive elements in various human tissues. The rich datasets described here will enhance our understanding of the mechanisms controlling tissue-specific gene expression programs. One replicate of Hi-C experiment in four human tissues with four different individuals (Thymus STL001, Aorta STL002, Leftventricle STL003, and Liver STL011).

2015-02-18 | E-GEOD-58752 | biostudies-arrayexpress

Integrative analysis of haplotype-resolved epigenomes across human tissues

2015-02-18 | GSE58752 | GEO

Thrombopoietin signaling to chromatin elicits rapid and pervasive epigenome remodeling within poised chromatin architectures

Project description:Thrombopoietin (TPO) is a critical cytokine regulating hematopoietic stem cell maintenance and differentiation into the megakaryocytic lineage. However, the transcriptional and chromatin dynamics elicited by TPO signaling are poorly understood. Here, we study the immediate early transcriptional and cis-regulatory responses to TPO in hematopoietic stem/progenitor cells (HSPCs) and use this paradigm of cytokine signaling to chromatin to dissect the relation between cis-regulatory activity and chromatin architecture. We show that TPO profoundly alters the transcriptome of HSPCs, with key hematopoietic regulators being transcriptionally repressed within 30 minutes of TPO. By examining cis-regulatory dynamics and chromatin architectures, we demonstrate that these changes are accompanied by rapid and extensive epigenome remodeling of cis-regulatory landscapes that is spatially coordinated within topologically associating domains (TADs). Moreover, homotypic TPO-responsive enhancers are spatially clustered and engage in preferential intra- and inter-TAD interactions that are only moderately perturbed by TPO signaling. By further examining the link between cis-regulatory dynamics and chromatin looping, we show that rapid modulation of cis-regulatory activity is largely independent of chromatin looping dynamics. Finally, we show that activated and repressed cis-regulatory elements share a remarkably similar DNA sequence composition and that in vivo transcription factor binding patterns accurately predict rapid cis-regulatory responses to TPO.

2018-01-25 | GSE100835 | GEO

Elucidating the Cellular and Molecular Dynamics of Sebaceous Gland Self-Renewal and Regeneration

Project description:We isolated murine sebaceous gland (SG) cells and performed highly targeted single cell RNA-sequencing (scRNA-seq) to identify novel cell subpopulations and to infer lineage relationships.

2023-08-08 | GSE225252 | GEO

Multi-omics gene regulatory network analysis of resting and stimulated PBMCs [PBMC isolate scRNA-seq]

Project description:Cells require coordinated control over gene expression changes when responding to environmental stimuli. Recent advancements in single-cell technologies have enabled studies of regulatory dynamics associated with cellular perturbation response in immune cells. However, associating these changes to underlying differences in epigenetic regulation through integration of multi-omic data has not been achieved at single-cell resolution. Here, we apply single-cell ATAC-seq (scATAC-seq) and scRNA-seq to assay chromatin accessibility and gene expression in resting and stimulated human blood cells. Collectively, we generate ~91,000 high-coverage single-cell profiles, allowing us to probe the cis-regulatory landscape of immunological response across cell types, stimuli and time. Advancing tools to integrate multiomic data, we connect distal cis-regulatory elements to genes, identifying key regulatory hubs associated with immune signaling and stress response. Subsequently, we design FigR - a method to infer gene regulatory networks (GRNs) to identify candidate TF regulators across single cells. Importantly, construction of a GRN using stimulus response data identifies TF regulatory activity associated with genetic variants in inflammatory diseases. Lastly, we assess the time-dependent regulatory dynamics of immune stimulation, where we find that cells alter chromatin accessibility prior to productive gene expression, a process occurring at time scales of minutes. Extending this concept of chromatin-mediated priming, and incorporating regulatory relationships defined by FigR, we detect a rare subpopulation of monocytes marked by a primed chromatin state predictive of enhanced immunological response. Overall, we build upon computational tools for GRN construction and demonstrate the utility of GRNs for analysis of multi-omic single cell data.

2022-06-20 | GSE178430 | GEO

Multi-omics gene regulatory network analysis of resting and stimulated PBMCs [stimulation scRNA-seq]

2022-06-20 | GSE178429 | GEO

Multi-omics gene regulatory network analysis of resting and stimulated PBMCs [scATAC-seq]

2022-06-20 | GSE178428 | GEO

Human lineage tracing enabled by mitochondrial mutations and single cell genomics [TF1_barcoding_ATAC]

Project description:Lineage tracing provides unprecedented insights into the fate of individual cells and their progeny in complex organisms. While effective genetic approaches have been developed in vitro and in animal models, these cannot be used to interrogate human physiology in vivo. Instead, naturally occurring somatic mutations have been utilized to infer clonality and lineal relationships between cells in human tissues, but current approaches are limited by high error rates and scale, and provide little information about the state or function of the cells. Here, we show how somatic mutations in mitochondrial DNA (mtDNA) can be tracked by current single cell RNA-Seq (scRNA-Seq) or single cell ATAC-Seq (scATAC-Seq) for simultaneous analysis of single cell lineage and state. We leverage somatic mtDNA mutations as natural genetic barcodes and demonstrate their use as clonal markers to infer lineal relationships. We trace the lineage of human cells by somatic mtDNA mutations in a native context both in vitro and in vivo, and relate it to expression profiles and chromatin accessibility. Our approach should allow lineage tracing at a 100- to 1,000-fold greater scale than with single cell whole genome sequencing, while providing information on cell state, opening the way to chart detailed cell lineage and fate maps in human health and disease.

2019-02-28 | GSE118202 | GEO

Human lineage tracing enabled by mitochondrial mutations and single cell genomics [TF1_barcoding_scRNA]

2019-02-28 | GSE118203 | GEO

Human lineage tracing enabled by mitochondrial mutations and single cell genomics [CRC_ATAC]

2019-02-28 | GSE122583 | GEO