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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Genetic variations accumulating within populations over generations give rise to biological evolution. Evolutionary changes can result in the formation of novel varieties and entire new species. These changes are responsible for the diverse forms of life inhabiting the planet. The evidence for evolution suggests that all living organisms descended from common ancestors.
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Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.
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The endosymbiont theory is the most widely accepted theory of eukaryotic evolution; however, its progression is still somewhat debated. According to the nucleus-first hypothesis, the ancestral prokaryote first evolved a membrane to enclose DNA and form the nucleus. Conversely, the mitochondria-first hypothesis suggests that the nucleus was formed after endosymbiosis of mitochondria.
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Updated: Jan 30, 2026

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Resolving clonal evolution and selection of extrachromosomal DNA at single-cell resolution.

Josephine Deleuran Hendriksen1,2,3, Alessio Locallo1,2,3, Balthasar Clemens Schlotmann1,2

  • 1The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Genome Biology
|January 29, 2026
PubMed
Summary

Extrachromosomal DNA (ecDNA) drives cancer growth and drug resistance. Our new computational method, ecSingle, reveals ecDNA's role in tumor heterogeneity and evolution at the single-cell level.

Keywords:
CancerClonal evolutionExtrachromosomal DNALong-read sequencingOncogene amplificationSingle cell

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Area of Science:

  • Genomics
  • Cancer Biology
  • Computational Biology

Background:

  • Extrachromosomal DNA (ecDNA) is crucial for cancer progression, influencing oncogene amplification, tumor growth, and drug resistance.
  • Intratumor heterogeneity and clonal selection driven by ecDNA remain poorly understood.
  • Understanding ecDNA dynamics is vital for developing effective cancer therapies.

Purpose of the Study:

  • To develop a novel computational approach for analyzing ecDNA heterogeneity at the single-cell level.
  • To investigate the clonal evolution and transcriptional cell states associated with ecDNA in cancer.
  • To provide deeper insights into the role of ecDNA in intratumor heterogeneity and cellular plasticity.

Main Methods:

  • Developed ecSingle, a computational method utilizing allelic imbalance and outlier expression from single-cell RNA sequencing (scRNA-seq).
  • Validated findings using genome sequencing and single-molecule long-read sequencing for superior ecDNA resolution.
  • Analyzed tumor samples to identify and characterize oncogene-carrying ecDNAs at the single-cell level.

Main Results:

  • Identified oncogene-carrying ecDNAs in tumor samples using the ecSingle approach.
  • Demonstrated extensive intratumor heterogeneity of ecDNA, with subclonal ecDNAs linked to distinct cell states.
  • Showcased how rare ecDNA-positive clones in primary tumors can expand to become dominant in relapsed tumors.

Conclusions:

  • Introduced a novel single-cell approach (ecSingle) for studying ecDNA, enabling clonal evolution and cell state analysis.
  • Gained significant insights into the contribution of ecDNA to intratumor heterogeneity and cancer cell plasticity.
  • Highlighted the potential of targeting ecDNA dynamics for cancer treatment strategies.