Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells

ABSTRACT: During mouse development, embryonic stage germ cells (EGCs) make crucial fate decisions, with female ones embark on meiosis whereas male ones enter mitotic arrest until birth. Despite the mounting knowledge about their reprogramming of epigenetic modifications, the dynamics of 3D genome structures within individual EGCs remains elusive. Herein, we presented a single-cell-input long-read Hi-C method, scNanoHi-C2, and systematically dissected the reprogramming dynamics of EGC chromatin structures. We found that, despite the similar attenuation of A/B compartments and topologically associating domains (TADs), and the appearance of refined A/B compartments in autosomes comparable to spermatogenesis, the X chromosomes of female EGCs showed enhanced specific interactions between B compartments probably due to their incomplete reactivation. By reconstructing single-cell 3D genome models, we revealed the dynamic chromosome positioning during meiosis at single-cell level, showing that the neighborhood between non-homologous chromosomes of EGCs was relatively random. At the same time, the transposable elements (TEs) underwent dramatic chromatin reorganization, and a preferential asymmetric distribution of Alu/B2 elements around the meiotic TAD boundaries emerged, which reflected the formation of refined-compartments, maintaining the balances between global chromatin condensation and local meiotic-specific transcription. Notably, we demonstrated the specific chromatin loop extrusion around recombination hotspots during meiosis, which may provide a structural basis facilitating reliable homologous recombination. We also revealed an unexpected chromatin structure in mitotic arrested male EGCs distinct from the previously assumed G0 status, which may prime the unique genome structure for subsequent spermatogenesis. Altogether, our study revealed key features of the chromatin structure reprogramming in EGCs, emphasizing the potential roles of 3D genome structures for mammalian germ cell development.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE269496 | GEO | 2025/05/10

REPOSITORIES: GEO