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Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity [4T1-Splenocyte]

ABSTRACT: Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity [4T1-Splenocyte]

PROVIDER: PRJNA445230 | ENA |

REPOSITORIES: ENA

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Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity

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Project description:Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity [K562_GATA2]

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Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity [Tumor_stained_for_EpCam_HIF1a]

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Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity [GM_MI-ATAC_unstained]

Project description:Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity [GM_MI-ATAC_unstained]

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Joint single-cell chromatin and protein profiling reveals environmental regulation of epigenomic heterogeneity [4T1-Splenocyte]

Project description:A novel scATAC-seq approach, Multi-Index single cell ATAC-seq (MI-ATAC), in which we not only index the accessible chromatin of individual cells, but also index their protein expression using index Fluorescence Activated Cell Sorting (FACS).

2018-11-09 | GSE112194 | GEO

Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity.

Project description:Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1? protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells.

| S-EPMC6214962 | biostudies-literature

Single-cell epigenomic variability reveals functional cancer heterogeneity

Project description:Background: Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity, but is difficult to detect and assess functionally. Results: We develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells. Fluorescence-activated cell sorting of CD24 high vs. low cells prospectively isolated GATA1 and GATA2 high vs. low cells. GATA high vs. low cells express differential gene regulatory networks, differential sensitivity to the drug imatinib mesylate, and differential self-renewal capacity. Lineage tracing experiments show that GATA/CD24hi cells have the capability to rapidly reconstitute the heterogeneity within the entire starting population, suggesting that GATA expression levels drive a phenotypically relevant source of epigenomic plasticity. Conclusion: Single-cell chromatin accessibility can guide prospective characterization of cancer heterogeneity. Epigenomic subpopulations in cancer impact drug sensitivity and the clonal dynamics of cancer evolution.

2016-12-12 | GSE76224 | GEO

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