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Updated: Jun 13, 2025
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
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Deciphering alternative splicing patterns during cell fate transition of fast chemical reprogramming
Yunkun Lu1,2, Kainan Lin3, Yeling Ruan4
1Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. kevenloo1@zju.edu.cn.
BMC Biology
|June 9, 2025
Summary
Fast chemical reprogramming (FCR) reveals dynamic alternative splicing (AS) patterns during cell fate transitions. Exon exclusion dominates, with Ptbp3 identified as a key splicing factor influencing epigenetic regulation.
Area of Science:
- Molecular Biology
- Genomics
- Cell Biology
Background:
- Alternative splicing (AS) significantly increases transcriptome complexity in eukaryotes.
- Fast chemical reprogramming (FCR) offers a novel method for rapid somatic cell to induced pluripotent stem cell (iPSC) conversion.
Purpose of the Study:
- To investigate the dynamics of alternative splicing (AS) during the cell fate transition induced by the Fast Chemical Reprogramming (FCR) system.
- To understand the interplay between gene expression and AS patterns during FCR.
- To compare AS patterns between FCR and transcription factor-induced reprogramming (TFR).
Main Methods:
- Utilized the FCR system to induce cell fate transition.
- Analyzed gene expression profiles to characterize the FCR trajectory.
- Examined alternative splicing patterns, including exon inclusion/exclusion and intron retention events.
Main Results:
- FCR trajectory, based on gene expression, correlated with observed AS patterns, indicating a regulatory interplay.
- Exon exclusion was more prevalent than exon inclusion during FCR.
- FCR exhibited distinct AS patterns compared to TFR, highlighting system-specific regulation.
- Polypyrimidine tract-binding protein 3 (Ptbp3) was identified as a potential splicing factor involved in late-stage epigenetic regulation.
- Decreased spliceosome activity led to intron retention, potentially downregulating diapause-related genes.
Conclusions:
- Provided a detailed characterization of AS during FCR, emphasizing its critical role in cell fate regulation.
- Advanced understanding of molecular mechanisms governing cell fate decisions.
- Offered insights into FCR's potential for regenerative medicine and therapeutic applications.
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