Three-dimensional Genome Structures of Single Diploid Human Cells

Science. 2018 Aug 31;361(6405):924-928. doi: 10.1126/science.aat5641. Epub 2018 Aug 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Alleles
  • Blood Cells / chemistry
  • Blood Cells / ultrastructure
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Nucleus / ultrastructure
  • Chromatin / chemistry
  • Chromatin / genetics
  • Chromatin / ultrastructure*
  • Chromosomes, Human, X / ultrastructure
  • DNA / chemistry
  • DNA / ultrastructure*
  • DNA Copy Number Variations
  • Diploidy*
  • Gene Expression Regulation
  • Genome, Human*
  • Genomic Imprinting*
  • Haplotypes
  • Humans
  • Imaging, Three-Dimensional / methods
  • Nucleic Acid Amplification Techniques
  • Nucleic Acid Conformation*
  • Protein Conformation
  • Single-Cell Analysis / methods


  • Chromatin
  • DNA