Single-cell multi-omic profiling of chromatin conformation and DNA methylation

The ability to profile epigenomic features in single cells is facilitating the study of the variation in transcription regulation at the single cell level. Single cell methods have also facilitated the generation of cell-type resolved transcriptomic and epigenetic profiles of lineages derived from complex heterogeneous samples. However, integrating different epigenetic features remain challenging, as many current methods profile a single data type at at time. Furthermore, some epigenetic features, such as 3D genome organization, are intrinsically variable between single cells of the same lineage, so it remains unclear how well these methods may resolve cell-types from complex mixtures. Here we describe a method for profiling 3D genome organization and DNA methylation in single cells. This protocol accompanies Lee et al. (Nature Methods 2019) after peer review to aid potential users in applying the method to their own samples.

在单细胞中分析表观基因组特征的能力促进了单细胞水平转录调控变异的研究。单细胞方法还有助于从复杂的异质性样本中产生细胞类型分辨的转录组和表观遗传图谱。然而，整合不同的表观遗传特征仍然具有挑战性，因为许多当前的方法一次只能分析一种数据类型。此外，一些表观遗传特征，例如三维基因组结构，在同一谱系的单细胞之间本质上是可变的，所以这些方法从复杂混合物中分辨细胞类型的效果如何仍不清楚。在此我们描述一种在单细胞中分析三维基因组结构和DNA甲基化的方法。本实验方案在经过同行评审后随Lee等人（《自然方法》2019年）的研究一同发表，以帮助潜在用户将该方法应用于他们自己的样本。