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Creative Biolabs is a genomic and epigenomic research company dedicated to providing top-quality technical services and solutions to researchers from academia, government and industry around the world. As a reliable partner offering full-service and fit-for-purpose single cell omics solutions, we are committed to accurate and flexible data for your program at single-cell level.

Epigenetics

Epigenetics involves the study of regulatory systems that enable heritable changes in gene expression within genotypically identical cells. This includes chemical modifications to DNA and related histone proteins, as well as changes in chromatin accessibility and chromatin conformation. Emerging single cell epigenomic methods are being developed with the exciting potential to transform our knowledge of gene regulation. Single Cell has extensive expertise and advanced platforms in pyrosequencing, bisulfite sequencing, and various epigenomic research analysis techniques derived from our years of experience in the industry. We offer comprehensive suite of epigenomics platforms including:

Single Cell Methylation Sequencing (Methyl-Seq) Platform

DNA methylation is an epigenetic modification that plays a key role in regulating gene expression, thus affecting a variety of biological processes and diseases. The advances in single cell Methyl-Seq technologies allow for genome-wide profiling of methyl marks at single nucleotide and single cell resolutions. Genome-wide, single cell resolution DNA methylation analysis is now easily achieved using our comprehensive Methyl-Seq sequencing services. Our single cell Methyl-Seq platform can provide a wealth of useful DNA methylation information with detailed data parsed by our expert bioinformatics scientists.

Our single cell Methyl-Seq covers:

  • Single cell genome-wide CpG island (CGI) site Methyl-Seq
  • Single cell bisulfite sequencing
  • Single cell reduced-representation bisulfite sequencing
  • High, low, and premix methylation controls
  • Comprehensive data validation and analysis

Single cell DNA methylation analysis. Fig.1 Single cell DNA methylation analysis. (Schwartzman, 2015)

Single Cell Histone Modification Sequencing Platform

Histones can carry a diversity of covalent modifications that are functionally involved in regulating genomic characteristics and transcriptional states. These histone marks are typically mapped using chromatin immunoprecipitation sequencing (ChIP-seq), however, performing ChIP-seq at single-cell level is extremely challenging due to background noise. To solve this problem, Single Cell processed genomic DNA from a single cell pool by micrococcal nuclease (MNase) digestion and barcoding steps before the immunoprecipitation step. This improved approach enables pull-down to be effectively performed on thousands of cells. In addition to single cell ChIP-seq (scChIP-seq), other histone modification sequencing methods, such as DNA adenine methyltransferase identification sequencing (DamID-seq) and antibody-guided chromatin tagmentation sequencing (ACT-Seq), are also available at Single Cell.

Single Cell Chromatin Accessibility Sequencing Platform

Transcriptional activation results in disruption of nucleosome organization at promoters, enhancers, silencers, insulators and locus control regions due to transcription factor binding. Therefore, these regulatory DNA regions are consistent with the open/accessible genomic sites of remodeled chromatin. Mapping of these accessible chromatin regions helps to understand the regulation of gene expression, cell proliferation and differentiation, functional diversification and disease development. Several techniques have been developed to map accessible chromatin regions in a single cell. At Single Cell, we offer two techniques for mapping single cell chromatin accessibility.

  • Single cell Assay for Transposase-Accessible Chromatin (scATAC-seq): It uses the prokaryotic Tn5 transposase to tag regulatory regions by inserting sequencing adapters into accessible regions of the genome. In scATAC-seq, individual cells are captured and assayed using a programmable microfluidics platform with methods optimized for this task (Fig.2).
  • DNase I-based single-cell sequencing (scDNase-seq): This method is based on the fact that open/accessible chromatin regions are vulnerable to DNase I digestion. This technique offers a high sequencing resolution (300,000 mapped reads per single cell).

Workflow for measuring chromatin accessibility using scATAC-seq on a microfluidic device. Fig.2 Workflow for measuring chromatin accessibility using scATAC-seq on a microfluidic device. (Buenrostro, 2015)

Single Cell Chromatin Conformation Sequencing Platform

In addition to characterizing the linear chromatin organization of single cells, the study of chromosomal conformation is also important because the three-dimensional topology of chromosomes determines the interactions of gene promoters with enhancers, silencers, and insulators. A genome-scale technique called Hi-C has been developed to define the conformation of chromosomes. In Hi-C, chromatin DNA is immobilized and then digested by sequence-specific restriction enzymes while maintaining intact protein-protein and protein-DNA interactions. Re-ligation of digested DNA ends produces DNA chimaeras that retain spatial proximity interactions between different genomic loci. Given that Hi-C analysis of bulk cell populations may lead to some ambiguity in the interpretation of the results, single cell Hi-C (scHiC) has been developed as a cutting-edge technique to assess chromosomal conformation in a single cell. scHiC provides an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease.

Highlights

Based on the above platforms, Single Cell offers comprehensive solutions and customized services for single cell epigenomic analysis to meet the various needs of our customers. We deliver:

  • Superior technical expertise in genomic and epigenomic technologies, specializing in quantitative methylation analysis
  • The unparalleled quality of service for the academic and industrial communities worldwide
  • End-to-end service with bioinformatic analysis included at no additional charge
  • High-quality, accurate and publishable data
  • Customized experimental design and analysis services, including thousands of ready-to-use assay databases
  • Highest quality technical support and consultation from the design phase through project completion and data delivery
  • Post-completion technical support to assist with data analysis

If you have additional requirements or questions, please feel free to contact us.

References

  1. Schwartzman, O.; Tanay, A. Single-cell epigenomics: techniques and emerging applications. Nature Reviews Genetics. 2015.
  2. Buenrostro, J. D.; et al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature. 2015, 523(7561):486-490.
! ! For research purposes only. Not for clinical, therapeutic, or diagnostic purposes in animals or humans.

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