Journal Article

Three-dimensional genome structures of single diploid human cells

Xie, X. Sunney, Tan, Longzhi, Chang, Chi-Han, Li, Heng, Xing, Dong

2018

Overview

Beyond the sequence of the genome, its three-dimensional structure is important in regulating gene expression. To understand cell-to-cell variation, the structure needs to be understood at a single-cell level. Chromatin conformation capture methods have allowed characterization of genome structure in haploid cells. Now, Tan et al. report a method called Dip-C that allows them to reconstruct the genome structures of single diploid human cells. Their examination of different cell types highlights the tissue dependence of three-dimensional genome structures. Science , this issue p. 924 A single-cell chromatin conformation capture method employs transposon-based whole-genome amplification to detect chromatin contacts. Three-dimensional genome structures play a key role in gene regulation and cell functions. Characterization of genome structures necessitates single-cell measurements. This has been achieved for haploid cells but has remained a challenge for diploid cells. We developed a single-cell chromatin conformation capture method, termed Dip-C, that combines a transposon-based whole-genome amplification method to detect many chromatin contacts, called META (multiplex end-tagging amplification), and an algorithm to impute the two chromosome haplotypes linked by each contact. We reconstructed the genome structures of single diploid human cells from a lymphoblastoid cell line and from primary blood cells with high spatial resolution, locating specific single-nucleotide and copy number variations in the nucleus. The two alleles of imprinted loci and the two X chromosomes were structurally different. Cells of different types displayed statistically distinct genome structures. Such structural cell typing is crucial for understanding cell functions.

• Publisher: The American Association for the Advancement of Science
• Subject: Algorithms / Alleles / Amplification / Blood cells / Blood Cells - chemistry / Blood Cells - ultrastructure / Cell Line, Tumor / Cell Nucleus - genetics / Cell Nucleus - ultrastructure / Chromatin / Chromatin - chemistry / Chromatin - genetics / Chromatin - ultrastructure / Chromosomes / Chromosomes, Human, X - ultrastructure / Conformation / Copy number / Dependence / Diploidy / DNA - chemistry / DNA - ultrastructure / DNA Copy Number Variations / Gene expression / Gene Expression Regulation / Gene regulation / Genome, Human / Genomes / Genomic Imprinting / Haplotypes / Humans / Imaging, Three-Dimensional - methods / Literary Devices / Nucleic Acid Amplification Techniques / Nucleic Acid Conformation / Nucleotide sequence / Protein Conformation / Single-Cell Analysis - methods / Spatial discrimination / Spatial resolution / Structural analysis / Typing