Multi-omic analysis reveals dynamic changes of three-dimensional chromatin architecture during T cell differentiation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE210419 | GEO | 2023/07/02
REPOSITORIES: GEO
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Project description:Background: Activation of T cells results in widespread changes in transcriptional programs and multi-level remodeling of three-dimensional genome architecture. Although many efforts have been made in dissecting the epigenomic regulation during T cell activation and differentiation, it remains to be investigated in depth how alterations in the local and global chromatin structure coordinate gene expression in this process. Results: We characterize dynamic changes at different levels of chromatin organization during Naive CD4+ T (Naive) differentiation into T helper 17 (Th17) and T helper 1 (Th1) cells using Hi-C, RNA-Seq and ATAC-Seq assays. As a result of T cell activation, extensive changes occur at the transcriptome, chromatin accessibility and higher-order structure levels. We observe decreased short-range chromatin interactions and increased extra-long-range chromatin interactions upon activation. At compartment level, although A/B compartments have no apparent global switch, the intensity of compartmentalization markedly alters in activated T cells. At TAD level, a fraction of TADs is rearranged with increase TAD number upon activation. In addition, we identify promoter-enhancer (P-E) loops, many of which are associated with T cell activation or cell-type specificity, including Rorc encoding RORγt (retinoic-acid-receptor-related orphan receptor gamma t) that facilitates Th17 differentiation and Hif1a (hypoxia-inducible factor 1α) that responds to intracellular oxygen levels in Th1. Conclusion: T cell activation is conserved at multiple levels across T helper cells and species. From the 3D genome perspective, these results provide fresh insights into heterogeneity and plasticity of T helper cells during T cell activation based on chromatin reorganization.
2023-07-03 | GSE210416 | GEO
Project description:Background: Activation of T cells results in widespread changes in transcriptional programs and multi-level remodeling of three-dimensional genome architecture. Although many efforts have been made in dissecting the epigenomic regulation during T cell activation and differentiation, it remains to be investigated in depth how alterations in the local and global chromatin structure coordinate gene expression in this process. Results: We characterize dynamic changes at different levels of chromatin organization during Naive CD4+ T (Naive) differentiation into T helper 17 (Th17) and T helper 1 (Th1) cells using Hi-C, RNA-Seq and ATAC-Seq assays. As a result of T cell activation, extensive changes occur at the transcriptome, chromatin accessibility and higher-order structure levels. We observe decreased short-range chromatin interactions and increased extra-long-range chromatin interactions upon activation. At compartment level, although A/B compartments have no apparent global switch, the intensity of compartmentalization markedly alters in activated T cells. At TAD level, a fraction of TADs is rearranged with increase TAD number upon activation. In addition, we identify promoter-enhancer (P-E) loops, many of which are associated with T cell activation or cell-type specificity, including Rorc encoding RORγt (retinoic-acid-receptor-related orphan receptor gamma t) that facilitates Th17 differentiation and Hif1a (hypoxia-inducible factor 1α) that responds to intracellular oxygen levels in Th1. Conclusion: T cell activation is conserved at multiple levels across T helper cells and species. From the 3D genome perspective, these results provide fresh insights into heterogeneity and plasticity of T helper cells during T cell activation based on chromatin reorganization.
2023-07-03 | GSE210418 | GEO
Project description:Background: Activation of T cells results in widespread changes in transcriptional programs and multi-level remodeling of three-dimensional genome architecture. Although many efforts have been made in dissecting the epigenomic regulation during T cell activation and differentiation, it remains to be investigated in depth how alterations in the local and global chromatin structure coordinate gene expression in this process. Results: We characterize dynamic changes at different levels of chromatin organization during Naive CD4+ T (Naive) differentiation into T helper 17 (Th17) and T helper 1 (Th1) cells using Hi-C, RNA-Seq and ATAC-Seq assays. As a result of T cell activation, extensive changes occur at the transcriptome, chromatin accessibility and higher-order structure levels. We observe decreased short-range chromatin interactions and increased extra-long-range chromatin interactions upon activation. At compartment level, although A/B compartments have no apparent global switch, the intensity of compartmentalization markedly alters in activated T cells. At TAD level, a fraction of TADs is rearranged with increase TAD number upon activation. In addition, we identify promoter-enhancer (P-E) loops, many of which are associated with T cell activation or cell-type specificity, including Rorc encoding RORγt (retinoic-acid-receptor-related orphan receptor gamma t) that facilitates Th17 differentiation and Hif1a (hypoxia-inducible factor 1α) that responds to intracellular oxygen levels in Th1. Conclusion: T cell activation is conserved at multiple levels across T helper cells and species. From the 3D genome perspective, these results provide fresh insights into heterogeneity and plasticity of T helper cells during T cell activation based on chromatin reorganization.
2023-07-03 | GSE210417 | GEO
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Project description:We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes. These expression data are used in the paper to show that there are marked differences in mRNA expression between loci in the open and closed chromatin compartments. Experiment Overall Design: Affy Expression array for GM06690 cells
2009-10-10 | E-GEOD-18350 | biostudies-arrayexpress
Project description:Mammalian erythroid cells development can be divided into three period: hematopoietic stem and progenitor cells (HSPC), erythroid progenitor (Ery-Pro) and erythroid precursor (Ery-Pre). To better understand human erythropoiesis and its regulation, we performed genome-wide studies of chromatin architecture, enhancer and select transcription factors binding, and transcriptomics profiling utilizing modified strategy to obtain defined progenitor and precursor populations from primary human erythroid cells. Integration and analysis of these data reveals that the TAD structure is stable but promoter - enhancer interactions are highly dynamic in a stage specific manner. Erythroid master regulator - GATA1 involves in the P-E interactions stepwisely. GATA1 binding is largely stable in erythroid progenitor and precursor, but dynamic GATA1 binding during this process regulate a productive erythroid gene expression and local chromatin rewiring. Additionally, we also have showed that dosage of GATA1 control the erythroid progenitor behavior and the erythroid progression. The valuable chromatin architecture and epigenome data will provide more comprehensive insight of human erythropoiesis and dynamic gene regulation of cellular differentiation even more broadly.
2023-05-07 | GSE214808 | GEO
Project description:Mammalian erythroid cells development can be divided into three period: hematopoietic stem and progenitor cells (HSPC), erythroid progenitor (Ery-Pro) and erythroid precursor (Ery-Pre). To better understand human erythropoiesis and its regulation, we performed genome-wide studies of chromatin architecture, enhancer and select transcription factors binding, and transcriptomics profiling utilizing modified strategy to obtain defined progenitor and precursor populations from primary human erythroid cells. Integration and analysis of these data reveals that the TAD structure is stable but promoter - enhancer interactions are highly dynamic in a stage specific manner. Erythroid master regulator - GATA1 involves in the P-E interactions stepwisely. GATA1 binding is largely stable in erythroid progenitor and precursor, but dynamic GATA1 binding during this process regulate a productive erythroid gene expression and local chromatin rewiring. Additionally, we also have showed that dosage of GATA1 control the erythroid progenitor behavior and the erythroid progression. The valuable chromatin architecture and epigenome data will provide more comprehensive insight of human erythropoiesis and dynamic gene regulation of cellular differentiation even more broadly.
2023-05-07 | GSE214807 | GEO
Project description:The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional (2D) monolayers on plastic. However, many cellular features are impaired in these unnatural conditions and big alterations in gene expression in comparison to tumors have been reported. Three-dimensional (3D) cell culture models have become increasingly popular and are suggested to be better models than 2D monolayers due to improved cell-to-cell contacts and structures that resemble in vivo architecture. The aim of this study was to compare gene expression patterns of MCF7 breast cancer cells when grown as xenografts, in 2D, in polyHEMA coated anchorage independent 3D models and in Matrigel on-top 3D cell culture models. Surprisingly small variations in gene expression patterns were observed between the models indicating that 3D and xenograft are not always that different from 2D cell cultures. Gene expression analysis of MCF7 breast cancer cells cultured as xenografts for 43 days, in two dimensional cultures for seven days (2D7d), in polyHEMA three dimensional cell culture models for four and seven days (PH7d and PH7d), and in Matrigel three dimensional cultures for four and seven days (MG4d and MG7d). Two biological replicates was included for each sample.
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