Sci-Hi-C: A single-cell Hi-C method for mapping 3D genome organization in large number of single cells

Methods. 2020 Jan 1;170:61-68. doi: 10.1016/j.ymeth.2019.09.012. Epub 2019 Sep 16.


The highly dynamic nature of chromosome conformation and three-dimensional (3D) genome organization leads to cell-to-cell variability in chromatin interactions within a cell population, even if the cells of the population appear to be functionally homogeneous. Hence, although Hi-C is a powerful tool for mapping 3D genome organization, this heterogeneity of chromosome higher order structure among individual cells limits the interpretive power of population based bulk Hi-C assays. Moreover, single-cell studies have the potential to enable the identification and characterization of rare cell populations or cell subtypes in a heterogeneous population. However, it may require surveying relatively large numbers of single cells to achieve statistically meaningful observations in single-cell studies. By applying combinatorial cellular indexing to chromosome conformation capture, we developed single-cell combinatorial indexed Hi-C (sci-Hi-C), a high throughput method that enables mapping chromatin interactomes in large number of single cells. We demonstrated the use of sci-Hi-C data to separate cells by karytoypic and cell-cycle state differences and to identify cellular variability in mammalian chromosomal conformation. Here, we provide a detailed description of method design and step-by-step working protocols for sci-Hi-C.

Keywords: Chromatin; Chromosome; Hi-C; Sci-Hi-C; Single cell; Single-cell Hi-C; Three-dimensional (3D) genome architecture.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Separation / methods
  • Chromatin / genetics
  • Chromatin / isolation & purification
  • Chromatin / metabolism
  • Chromosome Mapping / methods*
  • Computer Simulation
  • Gene Library
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Mice
  • Nucleic Acid Conformation
  • Single-Cell Analysis / methods*


  • Chromatin