BdLT-Seq as a barcode decay-based method to unravel lineage-linked transcriptome plasticity

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.