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  • 1Cell Plasticity & Epigenetics Lab, Cancer Research UK - Manchester Institute, The University of Manchester, SK10 4TG, Manchester, UK.

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|February 25, 2023
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Summary

This study introduces Barcode decay Lineage Tracing-Seq (BdLT-Seq), a novel technology for observing cell plasticity. BdLT-Seq reveals how cell states are inherited and reshaped, generating non-genetic diversity crucial for adaptation.

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Area of Science:

  • Cellular and Molecular Biology
  • Developmental Biology
  • Genomics

Background:

  • Cell plasticity is fundamental to development and evolution.
  • Cellular systems maintain homeostasis by balancing meta-stable states.
  • Direct observation of meta-state dynamics and their role in generating clonal diversity is lacking.

Purpose of the Study:

  • To develop a lineage-tracing technology for observing cell plasticity dynamics.
  • To directly link non-genetic molecular features to phenotypic output.
  • To investigate the inheritance and reshaping of cell transcriptome states.

Main Methods:

  • Development of Barcode decay Lineage Tracing-Seq (BdLT-Seq).
  • Utilizing episome-encoded molecular identifiers with dynamic decay.
  • Tracking cell lineage directionality and phenotypic output in comparable genomic landscapes.

Main Results:

  • Cell transcriptome states are inherited and dynamically reshaped according to lineage rules.
  • This process occurs under basal growth, oncogene activation, and reversible therapeutic resistance.
  • BdLT-Seq demonstrates how intra-clonal non-genetic diversity is generated.

Conclusions:

  • BdLT-Seq provides a direct method to study cell plasticity and meta-state dynamics.
  • Understanding these dynamics is key to explaining non-genetic clonal diversity.
  • This technology offers insights into cellular adaptation and phenotypic variation.