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Defining heritability, plasticity, and transition dynamics of cellular phenotypes in somatic evolution
Joshua S Schiffman1,2, Andrew R D'Avino3,4,5, Tamara Prieto3,4
1New York Genome Center, New York, NY, USA. jschiffman@nygenome.org.
Nature Genetics
|September 24, 2024
Summary
This study introduces PATH, a new framework to quantify cell state heritability and plasticity using single-cell lineage tracing. PATH reveals insights into cell state transitions and proliferation dynamics in cancer evolution.
Area of Science:
- Genomics
- Developmental Biology
- Cancer Research
Background:
- Single-cell sequencing reveals cell state heterogeneity in tissues.
- The heritability and plasticity of these cell states are not well understood.
Purpose of the Study:
- Introduce PATH (phylogenetic analysis of trait heritability) to quantify cell state heritability versus plasticity.
- Infer cell state transition and proliferation dynamics from single-cell lineage tracing data.
Main Methods:
- Developed the PATH framework for analyzing single-cell lineage tracing data.
- Applied PATH to mouse models of pancreatic cancer, primary glioblastoma, and B cell acute lymphoblastic leukemia.
Main Results:
- Observed cell state heritability at the extremes of epithelial-to-mesenchymal transition in pancreatic cancer.
- Identified bidirectional transitions between stem- and mesenchymal-like cells in glioblastoma via astrocyte-like states.
- Reconstructed phylogenies to link B cell differentiation states with genetic drivers in leukemia.
Conclusions:
- PATH provides quantitative measures for cell state plasticity and heritability.
- The framework offers new insights into somatic evolution and cell state dynamics in cancer.
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