Renji Hospital, Key Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Clin Transl Med. 2022 Jun;12(6):e927. doi: 10.1002/ctm2.927.
During meiosis of mammalian cells, chromatin undergoes drastic reorganization. However, the dynamics of the three-dimensional (3D) chromatin structure during the development of female germline stem cells (FGSCs) are poorly understood.
The high-throughput chromosome conformation capture technique was used to probe the 3D structure of chromatin in mouse germ cells at each stage of FGSC development.
The global 3D genome was dramatically reorganized during FGSC development. In topologically associating domains, the chromatin structure was weakened in germinal vesicle stage oocytes and still present in meiosis I stage oocytes but had vanished in meiosis II oocytes. This switch between topologically associating domains was related to the biological process of FGSC development. Moreover, we constructed a landscape of chromosome X organization, which showed that the X chromosome occupied a smaller proportion of the active (A) compartment than the autosome during FGSC development. By comparing the high-order chromatin structure between female and male germline development, we found that 3D genome organization was remodelled by two different potential mechanisms during gamete development, in which interchromosomal interactions, compartments, and topologically associating domain were decreased during FGSC development but reorganized and recovered during spermatogenesis. Finally, we identified conserved chromatin structures between FGSC development and early embryonic development.
These results provide a valuable resource to characterize chromatin organization and for further studies of FGSC development.
在哺乳动物细胞的减数分裂过程中，染色质会经历剧烈的重组。然而，雌性生殖干细胞（FGSCs）发育过程中三维（3D）染色质结构的动态变化还知之甚少。
利用高通量染色体构象捕获技术探测了 FGSC 发育过程中各个阶段的小鼠生殖细胞的 3D 染色质结构。
在 FGSC 发育过程中，整个基因组的 3D 结构发生了剧烈重组。在拓扑关联域中，生殖泡期卵母细胞的染色质结构减弱，而在减数分裂 I 期卵母细胞中仍存在，但在减数分裂 II 期卵母细胞中已经消失。这种拓扑关联域之间的转换与 FGSC 发育的生物学过程有关。此外，我们构建了 X 染色体组织的图谱，显示 X 染色体在 FGSC 发育过程中比常染色体占据更小的活性（A）区比例。通过比较雌性和雄性生殖细胞发育的高级染色质结构，我们发现 3D 基因组组织在配子发育过程中通过两种不同的潜在机制进行重塑，其中 FGSC 发育过程中染色体间相互作用、区室和拓扑关联域减少，而在精子发生过程中重新组织和恢复。最后，我们鉴定了 FGSC 发育和早期胚胎发育之间的保守染色质结构。
这些结果为研究染色质组织和进一步研究 FGSC 发育提供了有价值的资源。
