2cChIP-seq: an efficient and reliable method for epigenomic profiling of small cell numbers and single cells [2cMeDIP-seq]

We developed a new technique by supplementing carrier materials during ChIP procedures (thereafter referred to as 2cChIP-seq), dramatically improving immunoprecipitation efficiency and reducing sample loss. Using 2cChIP-seq, we generated high-quality epigenomic profiles of histone modifications and DNA methylation in 10-1,000 cells. Moreover, 2cChIP-seq reliably captures genomic regions with histone modification at single-cell level. We characterized the methylome of differenting female germline stem cells (FGSCs) with this this approach. Through comparing the methylome patterns of undifferentiated and differentiating FGSCs, we observed a particular DNA methylation signature potentially involved in differentiation of mouse germline stem cells. Hence, we provide a robust and universal approach for epigenomic profiling starting with extremely lower input. Overall design: DNA methylation profiling analysis in GV oocytes with 2cMeDIP-seq