Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming
Abstract Background Alternative splicing (AS) is a substantial contributor to the high complexity of transcriptomes in multicellular eukaryotes. Fast chemical reprogramming (FCR) system is an innovative approach that facilitates the rapid transition of somatic cells into induced pluripotent stem cel...
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2025-06-01
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| Online Access: | https://doi.org/10.1186/s12915-025-02264-1 |
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| author | Yunkun Lu Kainan Lin Yeling Ruan Junjie Li Huizhen Zhang Tianyuan Pan Qianqian Wang Lianyu Lin Sijie Feng |
| author_facet | Yunkun Lu Kainan Lin Yeling Ruan Junjie Li Huizhen Zhang Tianyuan Pan Qianqian Wang Lianyu Lin Sijie Feng |
| author_sort | Yunkun Lu |
| collection | DOAJ |
| description | Abstract Background Alternative splicing (AS) is a substantial contributor to the high complexity of transcriptomes in multicellular eukaryotes. Fast chemical reprogramming (FCR) system is an innovative approach that facilitates the rapid transition of somatic cells into induced pluripotent stem cells (iPSCs). Results In this study, we used the FCR system to delve into the dynamics of AS during cell fate transition. The trajectory of FCR, as characterized by gene expression profiles, consistently aligned with that observed in AS patterns, revealing a complex interplay between AS and gene expression regulation. Additionally, we discovered that the exon exclusion events were more prevalent than the exon inclusion events, indicating a predominant mode of splicing regulation during FCR. Compared to transcription factor-induced reprogramming (TFR), FCR showed a distinct AS pattern, underscoring the unique regulatory mechanisms governing AS in each reprogramming system. Further investigation uncovered polypyrimidine tract-binding protein 3 (Ptbp3) as an important splicing factor, possibly participating in epigenetic regulation in late stage of FCR by affecting AS of epigenetic regulators. Moreover, we found an abundance of intron retention events caused by decrease in spliceosome activity, potentially contributing to the downregulation of key diapause-related genes in the middle and late stages of FCR. Conclusions This research provided a comprehensive characterization of AS during FCR, highlighting the pivotal roles of AS in regulating cell fate transitions. Our findings advanced the understanding of the molecular mechanisms governing cell fate decisions and offered new insights into the potential of FCR for regenerative medicine and therapeutic applications. |
| format | Article |
| id | doaj-art-b7ef8e169ba1442d8bcf0a689ece9a60 |
| institution | DOAJ |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-b7ef8e169ba1442d8bcf0a689ece9a602025-08-20T03:21:05ZengBMCBMC Biology1741-70072025-06-0123111610.1186/s12915-025-02264-1Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogrammingYunkun Lu0Kainan Lin1Yeling Ruan2Junjie Li3Huizhen Zhang4Tianyuan Pan5Qianqian Wang6Lianyu Lin7Sijie Feng8Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of MedicineDepartment of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Head and Neck Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of MedicineSchool of Medicine, Henan Polytechnic UniversitySchool of Medicine, Henan Polytechnic UniversityDepartment of General Medicine, the First Affiliated Hospital of Zhejiang University School of MedicineDepartment of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of MedicineCollege of Life Science, Fujian Agriculture and Forestry UniversityDepartment of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of MedicineAbstract Background Alternative splicing (AS) is a substantial contributor to the high complexity of transcriptomes in multicellular eukaryotes. Fast chemical reprogramming (FCR) system is an innovative approach that facilitates the rapid transition of somatic cells into induced pluripotent stem cells (iPSCs). Results In this study, we used the FCR system to delve into the dynamics of AS during cell fate transition. The trajectory of FCR, as characterized by gene expression profiles, consistently aligned with that observed in AS patterns, revealing a complex interplay between AS and gene expression regulation. Additionally, we discovered that the exon exclusion events were more prevalent than the exon inclusion events, indicating a predominant mode of splicing regulation during FCR. Compared to transcription factor-induced reprogramming (TFR), FCR showed a distinct AS pattern, underscoring the unique regulatory mechanisms governing AS in each reprogramming system. Further investigation uncovered polypyrimidine tract-binding protein 3 (Ptbp3) as an important splicing factor, possibly participating in epigenetic regulation in late stage of FCR by affecting AS of epigenetic regulators. Moreover, we found an abundance of intron retention events caused by decrease in spliceosome activity, potentially contributing to the downregulation of key diapause-related genes in the middle and late stages of FCR. Conclusions This research provided a comprehensive characterization of AS during FCR, highlighting the pivotal roles of AS in regulating cell fate transitions. Our findings advanced the understanding of the molecular mechanisms governing cell fate decisions and offered new insights into the potential of FCR for regenerative medicine and therapeutic applications.https://doi.org/10.1186/s12915-025-02264-1Alternative splicingFast chemical reprogrammingCell fate transitionDiapause-like state |
| spellingShingle | Yunkun Lu Kainan Lin Yeling Ruan Junjie Li Huizhen Zhang Tianyuan Pan Qianqian Wang Lianyu Lin Sijie Feng Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming BMC Biology Alternative splicing Fast chemical reprogramming Cell fate transition Diapause-like state |
| title | Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming |
| title_full | Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming |
| title_fullStr | Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming |
| title_full_unstemmed | Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming |
| title_short | Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming |
| title_sort | deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming |
| topic | Alternative splicing Fast chemical reprogramming Cell fate transition Diapause-like state |
| url | https://doi.org/10.1186/s12915-025-02264-1 |
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