DataVXAdvanced SciencePaper
journal article·2025-08Open access

Enhanced Activities of OCT4 and SOX2 Promote Epigenetic Reprogramming by Shortening G1 Phase

Lin Guo, Jiechun Lin, Qiwen Ren, Hao Sun, Yanhua Wu, Haofei Ge, Xiaolan Wu, Lihui Lin, Lining Liang, Changpeng Li, He Liu, Yuangbang Mai, Shilong Chu, Jiadong Liu, Jing Liu, Jiekai Chen, Duanqing Pei, Hui Zheng

Advanced Science· Volume 12· Issue 32
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Source abstract

Abstract

Abstract To investigate the interplay among OCT4, SOX2, and KLF4, the VP16 activation domain is fused to one or multiple of these factors during reprogramming. Fusion of VP16 with OCT4 and SOX2 (OvSvK) significantly increases the efficiency of induced pluripotent stem cell (iPSC) generation compared to other combinations. The enhanced activities of OCT4 and SOX2 directly facilitated reprogramming by activating downstream targets, some of which are involved in cell cycle regulation. This leads to a shortened G1 phase and a shift in cell cycle dynamics toward an iPSCs‐like state. Further analysis reveals that these cell cycle alterations reduced H3K27me3 levels on specific genes, thereby promoting reprogramming. Consistently, knockdown of Ccnd1 and Cdkn2a (si Ccnd1 , si Cdkn2a ) as well as overexpression of Ccne1 effectively shortened the G1 phase and enhanced reprogramming efficiency. These findings highlight the role of cell cycle modulation in epigenetic remodeling and provide mechanistic insights for optimization during somatic cell reprogramming.
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Research context

OpenAlex topics: Pluripotent Stem Cells Research · CRISPR and Genetic Engineering · Renal and related cancers

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Guangdong‐Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine GIBH‐CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510530 China

Joint School of Life Sciences Guangzhou Medical University Guangzhou 511436 China

University of Chinese Academy of Sciences Beijing 100049 China

Centre for Regenerative Medicine and Health Hong Kong Institute of Science & Innovation Chinese Academy of Sciences Hong Kong SAR 999077 China

Laboratory of Cell Fate Control School of Life Sciences Westlake University Hangzhou 310024 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Basic and Applied Basic Research Foundation of Guangdong Province · Science and Technology Planning Project of Guangdong Province

References (46)

Show source-provided references
1. 10.1016/j.cell.2006.07.02410.1016/j.cell.2006.07.024 ↗
2. 10.1038/nature0879710.1038/nature08797 ↗
3. 10.1126/science.abb007410.1126/science.abb0074 ↗
4. 10.1016/j.cell.2015.03.01710.1016/j.cell.2015.03.017 ↗
5. 10.1016/j.cell.2016.12.01610.1016/j.cell.2016.12.016 ↗
6. 10.1016/j.molcel.2019.01.04210.1016/j.molcel.2019.01.042 ↗
7. 10.1038/ncb276510.1038/ncb2765 ↗
8. 10.1038/335563a010.1038/335563a0 ↗
9. 10.1038/embor.2011.1110.1038/embor.2011.11 ↗
10. 10.1016/j.cub.2010.11.04910.1016/j.cub.2010.11.049 ↗
11. 10.1038/ncomms1516610.1038/ncomms15166 ↗
12. 10.1038/celldisc.2017.1710.1038/celldisc.2017.17 ↗
13. 10.1038/nature0859210.1038/nature08592 ↗
14. 10.1038/cr.2011.2810.1038/cr.2011.28 ↗
15. 10.1016/j.stem.2011.10.00510.1016/j.stem.2011.10.005 ↗
16. 10.1038/ng.280710.1038/ng.2807 ↗
17. 10.1161/CIRCRESAHA.115.30151710.1161/CIRCRESAHA.115.301517 ↗
18. 10.1074/jbc.M117.81045710.1074/jbc.M117.810457 ↗
19. 10.1038/s41422-020-0359-910.1038/s41422-020-0359-9 ↗
20. 10.1038/s41556-020-0487-y10.1038/s41556-020-0487-y ↗
21. 10.1016/j.molcel.2018.08.01010.1016/j.molcel.2018.08.010 ↗
22. 10.1038/nature0705610.1038/nature07056 ↗
23. 10.1016/j.cell.2009.01.00110.1016/j.cell.2009.01.001 ↗
24. 10.1038/s41556-019-0384-410.1038/s41556-019-0384-4 ↗
25. 10.1016/j.cell.2007.12.03310.1016/j.cell.2007.12.033 ↗
26. 10.1038/ng.249110.1038/ng.2491 ↗
27. 10.1016/j.stem.2011.10.00510.1016/j.stem.2011.10.005 ↗
28. 10.18637/jss.v031.i0710.18637/jss.v031.i07 ↗
29. 10.1016/j.celrep.2017.07.07110.1016/j.celrep.2017.07.071 ↗
30. 10.1093/nar/gkaa19710.1093/nar/gkaa197 ↗
31. 10.1016/j.stem.2017.10.01210.1016/j.stem.2017.10.012 ↗
32. 10.1016/j.cell.2012.09.04510.1016/j.cell.2012.09.045 ↗
33. 10.1016/j.stem.2010.04.01410.1016/j.stem.2010.04.014 ↗
34. 10.1093/molbev/msab07510.1093/molbev/msab075 ↗
35. 10.1016/j.stemcr.2018.07.00210.1016/j.stemcr.2018.07.002 ↗
36. 10.1093/nar/gkad59710.1093/nar/gkad597 ↗
37. 10.1016/j.stem.2021.04.02310.1016/j.stem.2021.04.023 ↗
38. 10.1016/j.cell.2018.10.04210.1016/j.cell.2018.10.042 ↗
39. 10.1038/s41556-024-01411-010.1038/s41556-024-01411-0 ↗
40. 10.1016/j.stemcr.2014.07.00610.1016/j.stemcr.2014.07.006 ↗
41. 10.1038/s41421-018-0074-610.1038/s41421-018-0074-6 ↗
42. 10.1038/s41580-018-0077-z10.1038/s41580-018-0077-z ↗
43. 10.1016/j.celrep.2017.04.06710.1016/j.celrep.2017.04.067 ↗
44. 10.1101/gad.289256.11610.1101/gad.289256.116 ↗
45. 10.1186/1471-2105-12-32310.1186/1471-2105-12-323 ↗
46. 10.1006/geno.2002.673210.1006/geno.2002.6732 ↗