Reconstitution of pluripotency from mouse fibroblast through Sall4 overexpression
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.
Authors
- Ping Zhu (ORCID: https://orcid.org/0000-0002-4276-9593)
- Jingxian Long
- Huiping Mao
- Lizhan Xiao (ORCID: https://orcid.org/0009-0005-9251-7801)
- Haokaifeng Wu (ORCID: https://orcid.org/0000-0001-8912-1199)
- Baojian Liao (ORCID: https://orcid.org/0000-0003-0229-7234)
- Runxia Lin
- Rongping Luo (ORCID: https://orcid.org/0000-0002-1608-1031)
- Jing Guo (ORCID: https://orcid.org/0000-0002-6399-3877)
- Lu‐Qin Wang (ORCID: https://orcid.org/0009-0000-8071-0093)
- Yi Li (ORCID: https://orcid.org/0000-0001-9292-8604)
- Jing Liu (ORCID: https://orcid.org/0000-0003-1600-7744)
- Zhen Zhang (ORCID: https://orcid.org/0000-0001-6286-8049)
- Manish Kumar (ORCID: https://orcid.org/0000-0002-3901-9679)
- Lihua Zeng (ORCID: https://orcid.org/0000-0002-8757-0510)
- Zixuan Wu (ORCID: https://orcid.org/0009-0006-4745-0000)
- Lihui Lin (ORCID: https://orcid.org/0009-0003-6041-9452)
- Yongzheng Yang
- Zifen Huang
Institutions
- Department of Health (CN)
- Chinese Academy of Sciences (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Guangdong Academy of Medical Sciences (CN)
- Guangdong Provincial People's Hospital (CN)
- Southern Medical University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-54924-5
- Citations
- 6
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Beijing Institute of Genomics, Chinese Academy of Sciences
- National Key Research and Development Program of China
- Science and Technology Planning Project of Guangdong Province
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
- Basic and Applied Basic Research Foundation of Guangdong Province