articleCellMay 1, 2022HYBRID OA

Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution

DYDian YangMGMatthew G. JonesSNSantiago NaranjoWMWilliam M. RideoutKHKyung Hoi Min

Howard Hughes Medical Institute · University of California, San Francisco · +13 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct…

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333
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23

Topics & keywords

Topics
Keywords
  • Biology
  • Somatic evolution in cancer
  • Lineage (genetic)
  • Viral phylodynamics
  • Epigenetics
  • Tumor progression
  • Epigenome
  • Phenotype
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