Genome wide LINE-1 profiling in single cells

Long interspersed element-1 (LINE-1), which comprise about 18% of the genome, is one of the most active and abundant mobile DNAs in the human genome. LINE-1 were the cause of some genetic diseases, and LINE-1 proteins were reported highly expressed in cancers. Our lab has been reported a genome wide LINE-1 mapping method, named transposon insertion profiling (TIP)-seq. Genome wide LINE-1 profiling of single cells could be useful for lineage tracing and has the potential to provide key insights in many field, such as cancer cell heterogeneity in malignancy, neuron cell diversity in human brain, or early embryo development. There have been significant barriers applying LINE-1 mapping to single cells, due to the chimeric artifacts and features of repetitive sequences. Here we demonstrated that TIP-seq is also useful for LINE-1 mapping in GM12878 single cells, evaluated the performance of different procedures, and compared them to TIP-seq in bulk DNA. The results showed that single cell TIPseq results agree with known GM12878 LINE-1 insertions, and among the several method we tested, MDA-D samples (MDA whole genome amplification followed by digesting the amplified genomic DNA with restriction enzymes in vectorette PCR) have the best performance in sensitivity of detecting L1Hs insertions.