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Updated: May 10, 2026

Optogenetic Signaling Activation in Zebrafish Embryos
Published on: October 27, 2023
Cell fate conversion by conditionally switching the signal-transducing domain of signalobodies
Yuichiro Tone1, Masahiro Kawahara, Jun Hayashi
1Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Abstract:
Conditionally and strictly controlling cell fates is important for biomedical applications including cell therapies. Although previous studies have been based on regulating the expression or activation of signaling molecules, the techniques therein require improvement in terms of reducing leakiness and complexity. In this study, we propose a novel cell fate converting system using our previously developed antibody/receptor chimeras named "signalobodies" in combination with a Cre/loxP recombination system. We designed a "switch vector" where a growth signalobody gene was flanked by two loxP sites and a death signalobody gene was placed downstream of the floxed cassette. Cells transduced with the switch vector showed superior growth activity in the presence of a specific antigen. Subsequent expression of Cre induced the death signalobody, leading to conditional cell death. This technology could be applicable for other cell fate conversion systems including differentiation and migration, by using appropriate signal-transducing domains.
Insights
This study introduces a novel cell fate control system using signalobodies and Cre/loxP recombination. It enables precise control over cell growth and death, crucial for advanced cell therapies.
Area of Science:
- Biotechnology
- Molecular Biology
- Cell Biology
Background:
- Precise control of cell fates is essential for biomedical applications like cell therapies.
- Existing methods for regulating cell signaling often suffer from leakiness and complexity.
Purpose of the Study:
- To develop a novel, highly controllable cell fate conversion system.
- To improve upon existing techniques for regulating cell signaling and fate.
Main Methods:
- Utilized antibody/receptor chimeras called "signalobodies".
- Developed a "switch vector" incorporating signalobody genes flanked by loxP sites.
- Combined the switch vector with a Cre/loxP recombination system for conditional gene expression.
Main Results:
- Cells transduced with the switch vector exhibited enhanced growth in the presence of a specific antigen.
- Cre expression triggered the activation of a death signalobody, leading to conditional cell death.
- Demonstrated a system with reduced leakiness and complexity compared to previous methods.
Conclusions:
- The developed signalobody and Cre/loxP system offers precise, conditional control over cell fates.
- This technology has potential applications in cell therapies, differentiation, and migration control.
- The system's modular design allows for adaptation to various signal-transducing domains for diverse cell fate conversions.
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