Three-dimensional genome structures of single mammalian sperm
The three-dimensional (3D) organization of chromosomes is crucial for packaging a large mammalian genome into a confined nucleus and ensuring proper nuclear functions in somatic cells. However, the packaging of the much more condensed sperm genome is challenging to study with traditional imaging or sequencing approaches. In this study, we develop an enhanced chromosome conformation capture assay, and resolve the 3D whole-genome structures of single mammalian sperm. The reconstructed genome structures accurately delineate the species-specific nuclear morphologies for both human and mouse sperm. We discover that sperm genomes are divided into chromosomal territories and A/B compartments, similarly to somatic cells. However, neither human nor mouse sperm chromosomes contain topologically associating domains or chromatin loops. These results suggest that the fine-scale chromosomal organization of mammalian sperm fundamentally differs from that of somatic cells. The discoveries and methods established in this work will be valuable for future studies of sperm related infertility.
Authors
- Shigang Zhao (ORCID: https://orcid.org/0000-0002-7407-9220)
- Keliang Wu (ORCID: https://orcid.org/0000-0001-9552-6096)
- Heming Xu (ORCID: https://orcid.org/0009-0004-3335-4216)
- Dong Xing (ORCID: https://orcid.org/0000-0002-8237-481X)
- Cheng Li (ORCID: https://orcid.org/0000-0002-1766-1409)
- Xiaowen Liu (ORCID: https://orcid.org/0000-0003-4139-1127)
- Hao Xie (ORCID: https://orcid.org/0000-0002-1328-8985)
- Han Zhao (ORCID: https://orcid.org/0000-0002-5127-8112)
- Yujie Chen (ORCID: https://orcid.org/0009-0004-3987-6138)
- Zhiyuan Liu (ORCID: https://orcid.org/0000-0002-2506-6925)
- Zi‐Jiang Chen (ORCID: https://orcid.org/0000-0001-6637-6631)
- Changjian Yin
- Yi Chi (ORCID: https://orcid.org/0009-0006-5967-751X)
Institutions
- Shandong University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Renji Hospital (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Institute for Reproductive Health (US)
- Shandong Maternal and Child Health Hospital (CN)
- Center for Life Sciences (CN)
- Shandong Academy of Chinese Medicine (CN)
- State Key Laboratory of Reproductive Medicine
- Tsinghua University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-23
- DOI
- https://doi.org/10.1038/s41467-025-59055-z
- Citations
- 11
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 8.87
Funders
- Shandong University
- National Natural Science Foundation of China
- Tsinghua University
- Peking University
- Shenzhen University
- Southern Medical University