Landscape control for cell fate transitions
Abstract Cell fate decision making is a core issue in systems biology with profound implications for cellular development and disease. Although dynamical system approaches using gene network models have advanced our knowledge of cell fate transitions, accurately and stably controlling these transiti...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Communications Physics |
| Online Access: | https://doi.org/10.1038/s42005-025-02160-8 |
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| _version_ | 1850137907650625536 |
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| author | Jinchao Lv Song Zhang Wenjia Zhou Chunhe Li |
| author_facet | Jinchao Lv Song Zhang Wenjia Zhou Chunhe Li |
| author_sort | Jinchao Lv |
| collection | DOAJ |
| description | Abstract Cell fate decision making is a core issue in systems biology with profound implications for cellular development and disease. Although dynamical system approaches using gene network models have advanced our knowledge of cell fate transitions, accurately and stably controlling these transitions remains a great challenge. Here, we present a landscape control (LC) approach based on energy landscape theory, which manipulates specific gene targets to direct cell fate. Through testing on a two-gene mutual inhibition and self-activation (MISA) model, an epithelial-mesenchymal transition (EMT) network, and a human embryonic stem cell (HESC) network, we demonstrate that LC significantly outperforms the previous optimal least action control (OLAC) approach in both effectiveness and computational efficiency. Moreover, LC can identify key transcription factors and integrate sparse control strategies to induce specific transitions. Overall, the LC framework provides a valuable tool for studying and engineering cell fate, with potential applications in therapeutic innovation and regenerative medicine. |
| format | Article |
| id | doaj-art-816f213ecedf46bca9b86c6dfa894f61 |
| institution | OA Journals |
| issn | 2399-3650 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Physics |
| spelling | doaj-art-816f213ecedf46bca9b86c6dfa894f612025-08-20T02:30:42ZengNature PortfolioCommunications Physics2399-36502025-06-018111110.1038/s42005-025-02160-8Landscape control for cell fate transitionsJinchao Lv0Song Zhang1Wenjia Zhou2Chunhe Li3Institute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityAcademy of Mathematics and Systems Science, Chinese Academy of SciencesInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan UniversityAbstract Cell fate decision making is a core issue in systems biology with profound implications for cellular development and disease. Although dynamical system approaches using gene network models have advanced our knowledge of cell fate transitions, accurately and stably controlling these transitions remains a great challenge. Here, we present a landscape control (LC) approach based on energy landscape theory, which manipulates specific gene targets to direct cell fate. Through testing on a two-gene mutual inhibition and self-activation (MISA) model, an epithelial-mesenchymal transition (EMT) network, and a human embryonic stem cell (HESC) network, we demonstrate that LC significantly outperforms the previous optimal least action control (OLAC) approach in both effectiveness and computational efficiency. Moreover, LC can identify key transcription factors and integrate sparse control strategies to induce specific transitions. Overall, the LC framework provides a valuable tool for studying and engineering cell fate, with potential applications in therapeutic innovation and regenerative medicine.https://doi.org/10.1038/s42005-025-02160-8 |
| spellingShingle | Jinchao Lv Song Zhang Wenjia Zhou Chunhe Li Landscape control for cell fate transitions Communications Physics |
| title | Landscape control for cell fate transitions |
| title_full | Landscape control for cell fate transitions |
| title_fullStr | Landscape control for cell fate transitions |
| title_full_unstemmed | Landscape control for cell fate transitions |
| title_short | Landscape control for cell fate transitions |
| title_sort | landscape control for cell fate transitions |
| url | https://doi.org/10.1038/s42005-025-02160-8 |
| work_keys_str_mv | AT jinchaolv landscapecontrolforcellfatetransitions AT songzhang landscapecontrolforcellfatetransitions AT wenjiazhou landscapecontrolforcellfatetransitions AT chunheli landscapecontrolforcellfatetransitions |