Epigenetics reloaded: the single-cell revolution

Bheda, Poonam; Schneider, Robert

doi:10.1016/j.tcb.2014.08.010

Cited by 57 publications

(45 citation statements)

References 75 publications

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“…ECs vs. myofibroblasts in skin biopsy), it is important to perform epigenetic studies in isolated cells as opposed to whole tissue or a mixture of cells such as PBMCs. The recent breakthrough in technologies allowing epigenomics analysis at a single cell level will indeed pushed the field toward further understanding how a cell maintains its phenotype, its lineage commitment, and how it is perturbed in a disease setting [169]. Finally, NGS technologies in the form of miRNA-seq can be utilized to profile genome-wide expression of the miRNA transcriptome.…”

Section: Conclusion and Future Prospectivementioning

confidence: 99%

Unfolding the pathogenesis of scleroderma through genomics and epigenomics

Tsou

Sawalha

2017

Journal of Autoimmunity

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With unknown etiology, scleroderma (SSc) is a multifaceted disease that comprises of immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated. The non-HLA genes associated with SSc are involved in various functions, with the most robust associations including genes for B and T cell activation and innate immunity. Other pathways include genes involved in extracellular matrix deposition, cytokines, and autophagy. Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 have the strongest associations with SSc. In addition to genetic predisposition, it became clear that environmental factors and epigenetic influences also contribute to the development of SSc. Epigenetics, which refers to studies that focus on heritable phenotypes resulting from changes in chromatin structure without affecting the DNA sequence, is one of the most rapidly expanding fields in biomedical research. Indeed extensive epigenetic changes have been described in SSc. Alteration in enzymes and mediators involved in DNA methylation and histone modification, as well as dysregulated miRNA levels all contribute to fibrosis, immune dysregulation, and impaired angiogenesis in this disease. Genes that were affected by epigenetic dysregulation include ones involved in autoimmunity, T cell function and regulation, TGFβ pathway, Wnt pathway, extracellular matrix, and transcription factors governing fibrosis and angiogenesis. In this review, we provide a comprehensive overview of the current findings of SSc genetic susceptibility, followed by an extensive description and a systematic review of epigenetic research that has been carried out to date in SSc. We also summarize the therapeutic potential of drugs that affect epigenetic mechanisms, and outline the future prospective of genomincs and epigenomics research in SSc.

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Section: Conclusion and Future Prospectivementioning

confidence: 99%

Unfolding the pathogenesis of scleroderma through genomics and epigenomics

Tsou

Sawalha

2017

Journal of Autoimmunity

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“…To elucidate the internal heterogeneity within complex tissues and cell populations, the development of single-cell methodology is desired. In spite of rapid development of single-cell technologies in other genomic fields (reviewed in [116, 117]), there has been so far no report for single-cell ChIP-seq analysis. Recently, the first method for collection of chromatin data at single-cell resolution was published [118].…”

Section: Future Potential: Single-cell Analysismentioning

confidence: 99%

Recent advances in ChIP-seq analysis: from quality management to whole-genome annotation

2016

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Chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis can detect protein/DNA-binding and histone-modification sites across an entire genome. Recent advances in sequencing technologies and analyses enable us to compare hundreds of samples simultaneously; such large-scale analysis has potential to reveal the high-dimensional interrelationship level for regulatory elements and annotate novel functional genomic regions de novo. Because many experimental considerations are relevant to the choice of a method in a ChIP-seq analysis, the overall design and quality management of the experiment are of critical importance. This review offers guiding principles of computation and sample preparation for ChIP-seq analyses, highlighting the validity and limitations of the state-of-the-art procedures at each step. We also discuss the latest challenges of single-cell analysis that will encourage a new era in this field.

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“…Indeed, gene expression has been revealed as an essentially stochastic process, resulting in cell-to-cell variations in mRNA and protein levels [54]. Single-cell biology, although a relatively young field, has already yielded many promising methods that have provided insights into the variability of cell populations, and many researchers are working on even more advanced techniques to look into singlecell dynamics [55,56]. The stochasticity of transcription observed in single-cell studies provides a very intriguing viewpoint, suggesting that there may be far more levels of regulation in play that lead to the deterministic pattern of expression observed at the population level [57,58].…”

Section: Data Interpretation and Future Directionsmentioning

confidence: 99%