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Conditional Reprogramming of Pediatric Human Esophageal Epithelial Cells for Use in Tissue Engineering and Disease Investigation
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Single-cell reveals age-dependent epithelial reprogramming and EMT vulnerability in THCA.

Qiankun Zhang1, Wei Pan2, Xiaohua Gong2

  • 1Department of Nephrology, The Fifth Affiliated Hospital of Wenzhou Medical University; Lishui Central Hospital; Lishui Hospital of Zhejiang University, Lishui, China.

Endocrine-Related Cancer
|May 22, 2026
PubMed
Summary

Thyroid cancer

Keywords:
PHTF2SNAI1epithelial–mesenchymal transitionsingle-cell RNA sequencingthyroid cancertumor microenvironment

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Thyroid cancer displays significant cellular heterogeneity.
  • Mechanisms of epithelial-mesenchymal transition (EMT) and tumor microenvironment (TME) remodeling are not fully understood.

Purpose of the Study:

  • To systematically characterize immune and epithelial heterogeneity in thyroid cancer.
  • To investigate the role of EMT in TME remodeling, immune evasion, and therapeutic resistance.

Main Methods:

  • Single-cell RNA sequencing of 92,849 cells from 20 thyroid tissue samples.
  • Cell type annotation, subclustering, and functional enrichment analyses.
  • Functional validation using shRNA-mediated knockdown in thyroid cancer cell lines.

Main Results:

  • Identified 26 distinct cell clusters with age- and stage-specific differences.
  • EMT-high tumors showed stromal enrichment, immune suppression, and activation of EMT drivers.
  • PHTF2 and SNAI1 knockdown inhibited proliferation and EMT markers; EMT-high tumors had altered drug sensitivity.

Conclusions:

  • PHTF2 and SNAI1 are key regulators of EMT and proliferation in thyroid cancer.
  • EMT-driven TME remodeling contributes to immune evasion and therapeutic resistance.
  • EMT-associated vulnerabilities present potential targets for precision therapy.