Most cited article - PubMed ID 39350302
Characterization of regeneration initiating cells during Xenopus laevis tail regeneration
Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME-mediated by cytokines such as IL-6, TGF-b, and galectins-further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME.
- Keywords
- CAF, IL-6, cancer, cancer-associated fibroblast, extracellular matrix, head and neck squamous cell carcinoma, immunity, stroma, therapy, tumour microenvironment,
- MeSH
- Squamous Cell Carcinoma of Head and Neck * immunology pathology MeSH
- Cancer-Associated Fibroblasts immunology pathology MeSH
- Papillomavirus Infections immunology complications MeSH
- Humans MeSH
- Neoplastic Stem Cells immunology pathology MeSH
- Tumor Microenvironment * immunology MeSH
- Head and Neck Neoplasms * immunology pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Embryos are regeneration and wound healing masters. They rapidly close wounds and scarlessly remodel and regenerate injured tissue. Regeneration has been extensively studied in many animal models using new tools such as single-cell analysis. However, until now, they have been based primarily on experiments assessing from 1 day post injury. RESULTS: In this paper, we reveal that critical steps initiating regeneration occur within hours after injury. We discovered the regeneration initiating cells (RICs) using single-cell and spatial transcriptomics of the regenerating Xenopus laevis tail. RICs are formed transiently from the basal epidermal cells, and their expression signature suggests they are important for modifying the surrounding extracellular matrix thus regulating development. The absence or deregulation of RICs leads to excessive extracellular matrix deposition and defective regeneration. CONCLUSION: RICs represent a newly discovered transient cell state involved in the initiation of the regeneration process.
- Keywords
- Xenopus laevis, RICs, ROCs, Regeneration,
- MeSH
- Single-Cell Analysis MeSH
- Extracellular Matrix metabolism MeSH
- Wound Healing MeSH
- Tail * MeSH
- Regeneration * MeSH
- Transcriptome MeSH
- Xenopus laevis * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH