Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency
Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown....
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/164884 |
| _version_ | 1826116835343335424 |
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| author | Ai, Zhipeng Xiang, Xinyu Xiang, Yangquan Szczerbinska, Iwona Qian, Yuli Xu, Xiao Ma, Chenyang Su, Yaqi Gao, Bing Shen, Hao Muhammad Nadzim Bin Ramli Chen, Di Liu, Yue Hao, Jia-Jie Ng, Huck Hui Zhang, Dan Chan, Yun-Shen Liu, Wanlu Liang, Hongqing |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Ai, Zhipeng Xiang, Xinyu Xiang, Yangquan Szczerbinska, Iwona Qian, Yuli Xu, Xiao Ma, Chenyang Su, Yaqi Gao, Bing Shen, Hao Muhammad Nadzim Bin Ramli Chen, Di Liu, Yue Hao, Jia-Jie Ng, Huck Hui Zhang, Dan Chan, Yun-Shen Liu, Wanlu Liang, Hongqing |
| author_sort | Ai, Zhipeng |
| collection | NTU |
| description | Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown. Here, we demonstrate the mechanism of how LTR7Ys, the human morula-blastocyst-specific HERVH long terminal repeats, are activated by the naive pluripotency transcription network. We find that KLF5 interacts with and rewires NANOG to bind and regulate LTR7Ys; in contrast, the primed-specific LTR7s are preferentially bound by NANOG in the absence of KLF5. The specific activation of LTR7Ys by KLF5 and NANOG in pluripotent stem cells contributes to human-specific naive pluripotency regulation. KLF5-LTR7Y axis also promotes the expression of trophectoderm genes and contributes to the expanded cell potential toward extra-embryonic lineage. Our study suggests that HERVs are activated by cell-state-specific transcription machinery and promote stage-specific transcription network and cell potency. |
| first_indexed | 2024-10-01T04:17:56Z |
| format | Journal Article |
| id | ntu-10356/164884 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:17:56Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1648842023-02-28T17:14:15Z Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency Ai, Zhipeng Xiang, Xinyu Xiang, Yangquan Szczerbinska, Iwona Qian, Yuli Xu, Xiao Ma, Chenyang Su, Yaqi Gao, Bing Shen, Hao Muhammad Nadzim Bin Ramli Chen, Di Liu, Yue Hao, Jia-Jie Ng, Huck Hui Zhang, Dan Chan, Yun-Shen Liu, Wanlu Liang, Hongqing School of Biological Sciences Genome Institute of Singapore Department of Biological Sciences, NUS Science::Biological sciences Cell Potency Naive and Primed Pluripotency Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown. Here, we demonstrate the mechanism of how LTR7Ys, the human morula-blastocyst-specific HERVH long terminal repeats, are activated by the naive pluripotency transcription network. We find that KLF5 interacts with and rewires NANOG to bind and regulate LTR7Ys; in contrast, the primed-specific LTR7s are preferentially bound by NANOG in the absence of KLF5. The specific activation of LTR7Ys by KLF5 and NANOG in pluripotent stem cells contributes to human-specific naive pluripotency regulation. KLF5-LTR7Y axis also promotes the expression of trophectoderm genes and contributes to the expanded cell potential toward extra-embryonic lineage. Our study suggests that HERVs are activated by cell-state-specific transcription machinery and promote stage-specific transcription network and cell potency. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This project is funded by the National Key Research and Development Program of China (2018YFC1005003), National Natural Science Foundation of China (31871372, 31950410535, 81974224, and 32170551), Zhejiang Provincial Natural Science Foundation of China (LZ22C120002 and LQ20C06004), Key Research and Development Program of Zhejiang Province (2021C03098), and the Singapore Ministry of Health’s National Medical Research Council Open Fund Individual Research Grant (OFIRG16nov021). 2023-02-22T02:44:50Z 2023-02-22T02:44:50Z 2022 Journal Article Ai, Z., Xiang, X., Xiang, Y., Szczerbinska, I., Qian, Y., Xu, X., Ma, C., Su, Y., Gao, B., Shen, H., Muhammad Nadzim Bin Ramli, Chen, D., Liu, Y., Hao, J., Ng, H. H., Zhang, D., Chan, Y., Liu, W. & Liang, H. (2022). Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency. Cell Reports, 40(8), 111240-. https://dx.doi.org/10.1016/j.celrep.2022.111240 2211-1247 https://hdl.handle.net/10356/164884 10.1016/j.celrep.2022.111240 36001968 2-s2.0-85136301707 8 40 111240 en OFIRG16nov021 Cell Reports © 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf |
| spellingShingle | Science::Biological sciences Cell Potency Naive and Primed Pluripotency Ai, Zhipeng Xiang, Xinyu Xiang, Yangquan Szczerbinska, Iwona Qian, Yuli Xu, Xiao Ma, Chenyang Su, Yaqi Gao, Bing Shen, Hao Muhammad Nadzim Bin Ramli Chen, Di Liu, Yue Hao, Jia-Jie Ng, Huck Hui Zhang, Dan Chan, Yun-Shen Liu, Wanlu Liang, Hongqing Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency |
| title | Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency |
| title_full | Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency |
| title_fullStr | Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency |
| title_full_unstemmed | Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency |
| title_short | Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency |
| title_sort | kruppel like factor 5 rewires nanog regulatory network to activate human naive pluripotency specific ltr7ys and promote naive pluripotency |
| topic | Science::Biological sciences Cell Potency Naive and Primed Pluripotency |
| url | https://hdl.handle.net/10356/164884 |
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