Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression
Abstract Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54924-5 |
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| author | Lizhan Xiao Zifen Huang Zixuan Wu Yongzheng Yang Zhen Zhang Manish Kumar Haokaifeng Wu Huiping Mao Lihui Lin Runxia Lin Jingxian Long Lihua Zeng Jing Guo Rongping Luo Yi Li Ping Zhu Baojian Liao Luqin Wang Jing Liu |
| author_facet | Lizhan Xiao Zifen Huang Zixuan Wu Yongzheng Yang Zhen Zhang Manish Kumar Haokaifeng Wu Huiping Mao Lihui Lin Runxia Lin Jingxian Long Lihua Zeng Jing Guo Rongping Luo Yi Li Ping Zhu Baojian Liao Luqin Wang Jing Liu |
| author_sort | Lizhan Xiao |
| collection | DOAJ |
| description | Abstract Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can induce iPSCs formation. Here, we report that SALL4 alone, under an optimized reprogramming medium iCD4, is capable of reprogramming mouse fibroblasts into iPSCs. Mechanistically, SALL4 facilitates reprogramming by inhibiting somatic genes and activating pluripotent genes, such as Esrrb and Tfap2c. Furthermore, we demonstrate that co-overexpressing SALL4 and OCT4 synergistically enhances reprogramming efficiency. Specifically, the activation of Rsk1/Esrrb/Tfap2c by SALL4, alongside OCT4’s activation of Sox2 and the suppression of Mndal by SALL4 and Sbsn by OCT4, cooperate to facilitate SALL4+OCT4-mediated reprogramming. Overall, our study not only establishes an efficient method for iPSCs induction using the SALL4 single factor but also provides insights into the synergistic effects of SALL4 and OCT4 in reprogramming. |
| format | Article |
| id | doaj-art-426ab1eab89845e7a71933d9c6f3ca63 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-426ab1eab89845e7a71933d9c6f3ca632025-01-05T12:34:56ZengNature PortfolioNature Communications2041-17232024-12-0115111810.1038/s41467-024-54924-5Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpressionLizhan Xiao0Zifen Huang1Zixuan Wu2Yongzheng Yang3Zhen Zhang4Manish Kumar5Haokaifeng Wu6Huiping Mao7Lihui Lin8Runxia Lin9Jingxian Long10Lihua Zeng11Jing Guo12Rongping Luo13Yi Li14Ping Zhu15Baojian Liao16Luqin Wang17Jing Liu18Center for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGuangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversitySchool of Basic Medical Sciences, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital of Guangzhou Medical UniversityCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCenter for Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesAbstract Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can induce iPSCs formation. Here, we report that SALL4 alone, under an optimized reprogramming medium iCD4, is capable of reprogramming mouse fibroblasts into iPSCs. Mechanistically, SALL4 facilitates reprogramming by inhibiting somatic genes and activating pluripotent genes, such as Esrrb and Tfap2c. Furthermore, we demonstrate that co-overexpressing SALL4 and OCT4 synergistically enhances reprogramming efficiency. Specifically, the activation of Rsk1/Esrrb/Tfap2c by SALL4, alongside OCT4’s activation of Sox2 and the suppression of Mndal by SALL4 and Sbsn by OCT4, cooperate to facilitate SALL4+OCT4-mediated reprogramming. Overall, our study not only establishes an efficient method for iPSCs induction using the SALL4 single factor but also provides insights into the synergistic effects of SALL4 and OCT4 in reprogramming.https://doi.org/10.1038/s41467-024-54924-5 |
| spellingShingle | Lizhan Xiao Zifen Huang Zixuan Wu Yongzheng Yang Zhen Zhang Manish Kumar Haokaifeng Wu Huiping Mao Lihui Lin Runxia Lin Jingxian Long Lihua Zeng Jing Guo Rongping Luo Yi Li Ping Zhu Baojian Liao Luqin Wang Jing Liu Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression Nature Communications |
| title | Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression |
| title_full | Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression |
| title_fullStr | Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression |
| title_full_unstemmed | Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression |
| title_short | Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression |
| title_sort | reconstitution of pluripotency from mouse fibroblast through sall4 overexpression |
| url | https://doi.org/10.1038/s41467-024-54924-5 |
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