Assume that a cell population contains 106 cells. We use beads-on-a-string model to represent the spatial organization of four loci (p1, p2, p3 and p4) in each cell. Assume that chromatin interaction between two loci can be measured by the Hi-C experiment only if the spatial distance between them is less than certain threshold (diameter of the dashed red circles). We further assume that the Hi-C experiment can be conducted on each single cell, and no chromatin interactions among p1, p2, p3 and p4 are observed except for the selected three cells (cell 1, cell 2 and cell 106). Within each cell, only one paired-end reads can be produced from two interacting loci pair. The observed Hi-C contact matrix is a population summation of cell specific Hi-C contact matrices, which correspond to multiple distinct 3D chromosomal structures.