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Abstract
Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs.
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1 Huazhong Agricultural University, Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Wuhan, China (GRID:grid.35155.37) (ISNI:0000 0004 1790 4137); Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, China (GRID:grid.419897.a) (ISNI:0000 0004 0369 313X)
2 Huazhong Agricultural University, Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Wuhan, China (GRID:grid.35155.37) (ISNI:0000 0004 1790 4137)
3 Yunnan University, Center for Life Sciences, School of Life Sciences, Kunming, China (GRID:grid.440773.3) (ISNI:0000 0000 9342 2456)
4 Huazhong Agricultural University, Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Wuhan, China (GRID:grid.35155.37) (ISNI:0000 0004 1790 4137); Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Key Laboratory of Agricultural Animal Genetics, Wuhan, China (GRID:grid.419897.a) (ISNI:0000 0004 0369 313X); Hubei Hongshan Laboratory, Wuhan, China (GRID:grid.419897.a)