Three-dimensional chromatin architecture of early-stage mouse embryos reconstructed via recurrence plots

Abstract

AbstractThe chromatin conformation capture-related methods such as Hi-C have improved our understanding of nuclear architecture and organization in recent years. However, reconstruction of nuclear architecture of individual cells from single cell Hi-C (scHi-C) data has been challenging due to limited information of DNA contacts owing to the low efficiency of DNA recovery from a single cell. We have previously developed an algorithm named as “recurrence plot-based reconstruction (RPR) method” for reconstructing three dimensional (3D) genomic structure from Hi-C data of single haploid cells1 and diploid cells 2. This mathematical method is based on a recurrence plot, a tool of nonlinear time series analysis for visualizing temporal patterns within a time series 3,4, and enables the reconstruction of a unique 3D chromosome architecture even from sparse (low-coverage) DNA contact information. Here we applied the RPR method to analyzing published scHi-C data of diploid cells derived from early-stage F1 hybrid embryos 5. We found that paternal and maternal chromosomes become gradually intermingled from 1 cell to 64 cell stage and that discrete chromosome territories (CTs) are largely established between 8 cell and 64 cell stages. We also observed Rabl-like polarized distribution of chromosomes from 2 cell to 8 cell stage but this polarization becomes mostly dissolved by 64 cell stage. The formation of Rabl-like configuration precedes rod-like extension of the chromosomal shape and their parallel alignment, implicating a role of Rabl-like configuration in avoiding entanglement and promoting effective mixing of chromosomes before establishment of CTs. We also found a cell-to-cell variability in chromatin configuration. Combination of scHi-C and RPR analyses thus can characterize distinct 3D chromatin architecture of individual cells at different developmental stages during early embryogenesis.