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

Abstract

The 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 from single-cell Hi-C (scHi-C) data is challenging due to limited information of DNA contacts obtained from a single cell. We have previously developed the Recurrence Plot-Based Reconstruction (RPR) method for reconstructing three dimensional (3D) genomic structure from Hi-C data of single haploid cells (1) and diploid cells (2). This algorithm is based on a recurrence plot, a tool of nonlinear time-series analysis for visualizing patterns within a time series (3, 4), and enables the reconstruction of a unique 3D chromosome architecture even from low-coverage DNA contact information. Here we used the RPR method to analyzing published scHi-C data of diploid cells derived from early-stage F1 hybrid embryos (5) as a proof-of-concept for understanding of global developmental changes in chromosomal architecture of early stage embryos. We found that paternal and maternal chromosomes become gradually intermingled from 1 cell to 64 cell stage, and that discrete chromosome territories are largely established between 8 cell and 64 cell stages. We also observed Rabl-like polarization of chromosomes from the 2-to 8-cell stages, but this polarization becomes mostly dissolved by the 64-cell stage. Rabl-like chromosome polarization precedes rod-like extension and parallel alignment of chromosomes, implicating the role of Rabl-like polarization in effective mixing of chromosomes before establishing chromosome territories. We also found cell-to-cell variability in chromatin configuration. A combination of scHi-C and RPR analyses can depict features of the 3D chromatin architecture of individual cells at different developmental stages during early embryogenesis.