Quartz-Seq

Whole-Transcript Amplification for Single Cells

The Quartz-Seq method optimizes whole-transcript amplification (WTA) of single cells (Sasagawa et al., 2013). In this method, an RT primer with a T7 promoter and PCR target is first added to the extracted mRNA. RT synthesizes first-strand cDNA, after which the RT primer is digested by exonuclease I. Next, a poly(A) tail is added to the 3′ ends of first-strand cDNA, along with a poly(dT) primer containing a PCR target. After second-strand generation, a blocking primer is added to ensure PCR enrichment in sufficient quantity for sequencing. Deep sequencing allows for accurate, high-resolution representation of the whole transcriptome of a single cell.

Similar methods: CEL-Seq, Drop-seq, MARS-Seq, CytoSeq, inDrop, Hi-SCL

Advantages:

  • Single-tube reaction suitable for automation
  • Digestion of RT primers by exonuclease I eliminates amplification of byproducts
  • Short fragments and byproducts are suppressed during enrichment

Disadvantages:

  • PCR biases can underrepresent GC-rich templates
  • Amplification errors caused by polymerases will be represented and sequenced incorrectly
  • Targets smaller than 500 bp are preferentially amplified by polymerases during PCR


Reagents:

Illumina Library prep and Array Kit Selector



Reviews:

Zhang X., Marjani S. L., Hu Z., Weissman S. M., Pan X. and Wu S. Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects. Cancer Res. 2016;76:1305-1312

Poulin J. F., Tasic B., Hjerling-Leffler J., Trimarchi J. M. and Awatramani R. Disentangling neural cell diversity using single-cell transcriptomics. Nat Neurosci. 2016;19:1131-1141

Sun H. J., Chen J., Ni B., Yang X. and Wu Y. Z. Recent advances and current issues in single-cell sequencing of tumors. Cancer Lett. 2015;365:1-10

Grun D. and van Oudenaarden A. Design and Analysis of Single-Cell Sequencing Experiments. Cell. 2015;163:799-810

Navin N. E. Cancer genomics: one cell at a time. Genome Biol. 2014;15:452

Liang J., Cai W. and Sun Z. Single-Cell Sequencing Technologies: Current and Future. J Genet Genomics. 2014;41:513-528



References:

Takeuchi M., Yamaguchi S., Sakakibara Y., et al. Gene expression profiling of granule cells and Purkinje cells in the zebrafish cerebellum. J Comp Neurol. 2016;

Archer N., Walsh M. D., Shahrezaei V. and Hebenstreit D. Modeling Enzyme Processivity Reveals that RNA-Seq Libraries Are Biased in Characteristic and Correctable Ways. Cell Syst. 2016;

Scialdone A., Natarajan K. N., Saraiva L. R., et al. Computational assignment of cell-cycle stage from single-cell transcriptome data. Methods. 2015;