Biology subjects

Cinat, D.

Publications and source records attributed to Cinat, D..

3 recordsLinked to original sources

bioRxiv2026

Radiation-induced interferon-I response impairs thyroid organoid function

Background and AimRadiotherapy is a standard cancer treatment, but radiation exposure to surrounding healthy tissues may lead to adverse side effects that compromise patient quality of life. In patients with head and neck cancer treated with radiotherapy, thyroid damage is a frequent complication, resulting in hypothyroidism or secondary thyroid malignancies. Although clinically recognized, the molecular mechanisms underlying these side effects remain mostly unexplored. This study aims to characterize the radiation-induced molecular alterations in thyroid organoids. MethodsBulk RNA sequencing was performed to investigate transcriptomic changes in tissue-derived thyroid organoids following gamma-irradiation. Observed changes were further validated and explored using qPCRs, western blotting, immunofluorescence, caspase 3/7 activity and organoid forming efficiency. ResultsOur findings identify interferon-{beta} (IFN-{beta}) signaling as a key mediator of radiation-induced inflammation in the thyroid. Additionally, the intrinsic apoptotic pathway was found to be the predominant mechanism of radiation-induced thyroid cell death. Notably, while IFN-{beta} exhibited a protective effect against apoptosis, it concurrently reduced thyroid stem progenitor cell potential. ConclusionsThese results highlight the dual role of IFN-{beta} signaling in modulating thyroid cell fate after irradiation, potentially promoting survival upon injury at the expense of regenerative potential.

cell biology↗

bioRxiv2024

Notch Signaling Drives Pro-Regenerative and Migratory Traits in Glandular Stem/Progenitor Cells

Organoid models have advanced our understanding of adult stem/progenitor cell dynamics and function. However, uncovering the regulatory mechanisms of scarce and often quiescent stem cells in organs like the salivary glands remains challenging. Using single-cell RNA sequencing and bulk ATAC and RNA-sequencing analysis, we conducted in-depth profiling of the cellular populations and key signaling pathways characterizing a mouse submandibular salivary gland organoid (mSGO) model at different temporal stages and in response to radiation damage. We identified Sox9- and Itgb1-expressing cells as the most primitive adult stem/progenitor populations and uncover novel stemness and migratory roles for Cd44-expressing cells. Moreover, we revealed that Notch signaling is essential for maintaining self-renewal and migration potential of these stem/progenitor cells post-irradiation. Extending these findings to patient-derived mSGOs, as well as murine and patient-derived mammary and thyroid gland organoids, we confirmed Notch signaling as a conserved regulator of stem/progenitor cell function under migrative and regenerative conditions.

cell biology↗

bioRxiv2024

Derepression of transposable elements enhances interferon beta signaling and stem/progenitor cell activity after proton irradiation.

Radiotherapy is a mainstay in cancer treatment, aiming to maximize DNA damage in tumors while minimizing harm to surrounding healthy tissues. However, the collateral damage to normal tissues, especially stem/progenitor cells essential for tissue regeneration and organ function, remains a significant challenge. Here, we investigate the molecular responses to photon and proton irradiation, two key modalities in head and neck cancer treatment, using organoids. Multiomics analysis reveals a stronger double-stranded RNA (dsRNA)-induced type I interferon (IFN-I) response following proton irradiation, driven by loss of heterochromatin regulators and derepression of transposable elements (TEs). This response, mediated by the cytoplasmic sensor RIG-I, enhances the inflammatory signaling initiated by the canonical dsDNA sensors cGAS and ZBP1. Genetic and pharmacological modulation of IFN-I signaling in vitro and in vivo demonstrates its critical role in enhancing stem/progenitor cell activity post-irradiation. Our findings reveal a pro-regenerative role of TE derepression-mediated IFN-I response suggesting this pathway as a promising therapeutic target to mitigate radiation-induced side effects. TeaserTransposable element-mediated type I interferon signaling enhances stem/progenitor cell activity after irradiation.

cell biology↗