van der Wal, R. | bioRxiv Science

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↗

bioRxiv2021

Towards rainy Arctic winters: experimental icing impacts tundra plant productivity and reproduction

The Arctic is warming rapidly, with winters warming up to seven times as fast as summers in some regions. Warm spells in winter lead to more frequent extreme rain-on-snow events that alter snowpack conditions and can encapsulate tundra vegetation in basal ice ( icing) for several months. However, tundra climate change studies have mainly focused on summer warming. Here, we investigate icing effects on vascular plant phenology, productivity, and reproduction in a pioneer field experiment in high Arctic Svalbard, simulating rain-on-snow and resultant icing in five consecutive winters, assessing vascular plant responses throughout each subsequent growing season. We also tested whether icing responses were modified by experimentally increased summer temperatures. Icing alone delayed early phenology of the dominant shrub, Salix polaris, but with evidence for a catch-up (through shortened developmental phases and increased community-level primary production) later in the growing season. This compensatory response occurred at the expense of delayed seed maturation and reduced community-level inflorescence production. Both the phenological delay and allocation trade-offs were associated with icing-induced lags in spring thawing and warming of the soil, crucial to regulating plant nutrient availability and acquisition. Experimental summer warming modified icing effects by advancing and accelerating plant phenology (leaf and seed development), thus increasing primary productivity already early in the growing season, and partially offsetting negative icing effects on reproduction. Thus, winter and summer warming must be considered simultaneously to predict tundra plant climate change responses. Our findings demonstrate that winter warm spells can shape high Arctic plant communities to a similar level as summer warming. However, the absence of accumulated effects over the years reveals an overall resistant community which contrasts with earlier studies documenting major die-off. As rain-on-snow events will be rule rather than exception in most Arctic regions, we call for similar experiments in coordinated circumpolar monitoring programmes across tundra plant communities.

plant biology↗