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Time-tagged ticker tapes for intracellular recordings
Dingchang Lin1,2, Xiuyuan Li3, Eric Moult3
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. dingchang@g.harvard.edu.
Nature Biotechnology
|January 2, 2023
Summary
Scientists engineered a protein fiber that acts as a ticker tape, recording cellular transcriptional history. This method allows precise timing of gene expression changes within individual cells over time.
Area of Science:
- Cellular biology
- Molecular biology
- Biotechnology
Background:
- Understanding cellular development and responses requires tracking gene expression over time.
- Existing methods for recording cellular histories often lack temporal precision or scalability.
Purpose of the Study:
- To develop a novel method for recording and precisely timing cellular transcriptional histories.
- To create an engineered protein-based system for high-resolution, single-cell temporal recording.
Main Methods:
- Engineered a protein fiber incorporating a HaloTag reporter for time-stamping growth with fluorescent dyes.
- Integrated a co-expressed eGFP tag, driven by a promoter of interest, to record transcriptional activation.
- Utilized high-resolution multi-spectral imaging and interpolation for accurate temporal analysis of recorded histories.
Main Results:
- Demonstrated successful recording of doxycycline-induced transcription in HEK cells.
- Showcased recording of cFos promoter activation in cultured neurons.
- Achieved single-cell absolute timing accuracy of 30-40 minutes over a 12-hour period.
Conclusions:
- The protein-based ticker tape provides a robust method for high-resolution temporal recording of cellular transcriptional events.
- This technology enables accurate mapping of gene expression dynamics within individual cells.
- The design is generalizable for massively parallel single-cell recordings of various physiological processes.
