3D Genomes of Single Diploid Human and Mouse Cells by Dip-C
The nucleus of a human diploid cell contains 46 chromosomes, 23 maternal and 23 paternal, together carrying 6 Gb of DNA, whose 3D structure is crucial for cellular functions. We used an improved chromatin conformation capture method and phased (haplotype-resolved) single-nucleotide polymorphisms (SNPs) to distinguish between the two haplotypes of each chromosome (Figure 1) and reconstructed the first 3D genomes from single diploid human and mouse cells. We term this method “diploid chromatin conformation capture” (Dip-C).
Fig. 1. The Dip-C Method. (Top) Schematic of the chromatin conformation capture protocol. Colors represent genomic coordinates. (Bottom) Imputation of the two chromosome haplotypes linked by each chromatin “contact†(red dots).
Fig. 2. 3D genome structures of single diploid human cells. (Top left) 3D genome structure of a representative cell. (Top right) Peculiar nuclear morphology in a cell that recently exited mitosis and in a cell with multiple nuclear lobes. (Bottom) Serial cross sections of a single cell showing compartmentalization of euchromatin (green) and heterochromatin (magenta), visualized by CpG frequency as a proxy.
Fig. 4. Cell type–specific chromatin structures. (Left) Four cell-type clusters can be distinguished by unsupervised clustering via PCA of single-cell chromatin compartments. (Right) An example region that was differentially compartmentalized between two cell types. Right panels visualize the configuration of the ~0.5-Mb region (thick yellow sticks) with respect to the rest of the genome (transparent, colored by CpG frequencies).
References
Tan, Longzhi; Xing, Dong; Chang, Chi-Han; Li, Heng; Xie, X. Sunney “Three-dimensional genome structures of single diploid human cells,” Science 43, 924-928. DOI:10.1126/science.aat5641 (2018)