RETrace: simultaneous retrospective lineage tracing and methylation profiling of single cells.

Genome Research
Christopher Jen-Yue Wei, Kun Zhang

Abstract

Retrospective lineage tracing harnesses naturally occurring mutations in cells to elucidate single cell development. Common single-cell phylogenetic fate mapping methods have utilized highly mutable microsatellite loci found within the human genome. Such methods were limited by the introduction of in vitro noise through polymerase slippage inherent in DNA amplification, which we characterized to be approximately 10-100× higher than the in vivo replication mutation rate. Here, we present RETrace, a method for simultaneously capturing both microsatellites and methylation-informative cytosines to characterize both lineage and cell type, respectively, from the same single cell. An important unique feature of RETrace was the introduction of linear amplification of microsatellites in order to reduce in vitro amplification noise. We further coupled microsatellite capture with single-cell reduced representation bisulfite sequencing (scRRBS), to measure the CpG methylation status on the same cell for cell type inference. When compared to existing retrospective lineage tracing methods, RETrace achieved higher accuracy (88% triplet accuracy from an ex vivo HCT116 tree) at a higher cell division resolution (lowering the required number of ...Continue Reading

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Citations

Jan 28, 2021·Journal of Developmental Biology·Shankar Rengasamy Venugopalan, Eric Van Otterloo
Mar 27, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xue BaiZhiwei Zhang
May 1, 2021·Journal of Cardiovascular Development and Disease·Joshua C PetersonMarco C DeRuiter
May 18, 2021·Current Opinion in Systems Biology·Lingfei WangLuca Pinello
Aug 7, 2021·Clinical Epigenetics·Nicholas D JohnsonJohanna K DiStefano
Mar 17, 2021·Annual Review of Genomics and Human Genetics·Gilad D EvronyChongyuan Luo

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