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A genetically encoded device for transcriptome storage in mammalian cells.

Yu-Kai Chao1,2, Michelle Wu1, Qiyu Gong1

  • 1Broad Institute of MIT and Harvard, Cambridge, MA, USA.

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Summary
This summary is machine-generated.

TimeVault is a new genetic tool that records cellular transcriptomes for days. This system helps scientists understand how cells respond to stress and evade therapies.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Linking past cellular states to future outcomes is crucial for understanding cell decisions.
  • Existing methods lack the ability to record dynamic molecular changes within living cells over extended periods.

Purpose of the Study:

  • To develop a genetically encoded system for recording and storing transcriptomes in mammalian cells.
  • To enable high-fidelity, transcriptome-wide analysis of cellular responses and fate decisions over time.

Main Methods:

  • Engineered vault particles were developed to capture mRNA via poly(A) binding protein.
  • The stability and fidelity of the stored transcriptome were assessed in living mammalian cells for over 7 days.
  • The system was used to capture transient stress responses and analyze gene expression in drug-naive persister lung cancer cells.

Main Results:

  • The TimeVault system demonstrated stable transcriptome storage within living cells for more than 7 days.
  • High-fidelity, transcriptome-wide recording was achieved with minimal cellular perturbation.
  • Transient stress responses and gene expression changes in EGFR inhibitor-evading lung cancer persister cells were successfully captured.

Conclusions:

  • TimeVault provides a powerful tool for linking past and present cellular states.
  • This technology aids in decoding cellular responses to stress, fate determination, and therapeutic resistance.
  • TimeVault opens new avenues for studying dynamic cellular processes and decision-making in real-time.