Biology subjects

Seco, J.

Publications and source records attributed to Seco, J..

7 recordsLinked to original sources

bioRxiv2026

An integrative cardio-informatics approach identifies positionally conserved ancestors of human lncRNA genes transcribed across vertebrate hearts

The poor conservation of lncRNA genes limits their comprehensive functional studies, as genetic engineering of relevant animal models presupposes the presence of corresponding defined orthologs. This limitation is prominently evident in cardiovascular research, where heart-related lncRNAs are rarely conserved between humans and other vertebrates, despite the highly conserved nature of cardiac function. Because lncRNAs frequently regulate neighboring protein-coding genes essential for cardomyocyte function (herein termed cardiomyocyte indispensable, CMIs), we hypothesized that they are under evolutionary pressure to retain their genomic position and transcriptional activity, irrespective of sequence similarities to prototypical human lncRNA genes. By integrating mouse cardiac knockout phenotypes with human single-cell transcriptomics data, we systematically identified heart-expressed CMIs and their neighboring. lncRNA genes. Cross-species synteny analyses revealed regions flanking 109 CMIs with conserved relative positions and transcriptional orientations across vertebrate genomes. As most of these loci reside within poorly annotated non-coding regions, we developed VertLncRNAchecker, a neural network-based web interface, that predicts lncRNA-like genes within these regions, which we termed positional ancestors. Finally, we validated in situ that these positional ancestors express mature lncRNA transcripts in the hearts of mice, pigs, and frogs, mirroring the expression of their human lncRNA counterparts. We present an accurate and retrainable computational platform for cross-species lncRNA discovery that prioritizes conserved genomic position over sequence conservation or existing genome annotations. This pipeline revealed putative ancestors of human heart-related lncRNAs hidden within the vertebrate non-coding dark genome, providing novel insights into lncRNA biology and evolution.

evolutionary biology↗

bioRxiv2026

Correlation of OCT-Based Radiomic Signatures With Dose-Associated Radiation Response in Tumor Spheroids

BackgroundThree-dimensional tumor spheroids are an established radiobiology model, but scalable, reproducible readouts of dose-dependent radiation response are lacking. We evaluated whether optical coherence tomography (OCT) radiomics can quantify dose-associated response in spheroids, and how it compares with conventional brightfield morphology. MethodsThis in vitro, cross-sectional study used SAS oral squamous cell carcinoma spheroids seeded at two densities (5000 and 10000 cells), irradiated at 0 to 12 Gy, and imaged on days 1 to 11 post-irradiation. Each OCT acquisition yielded co-registered structural-intensity and speckle-variance volumes. Radiomic features (shape, first-order, texture) were extracted with Radiomics.jl, filtered for repeatability, correlation-pruned, and ensemble-ranked. Dose correlation was assessed by repeated 5-fold cross-validation across five regressors, comparing brightfield-only (BF), OCT-only, and combined OCT+BF feature sets with paired Wilcoxon tests. ResultsOCT-only models consistently outperformed the BF baseline (median R2 0.77 to 0.85 versus 0.61 to 0.69; p < 0.001 for all regressors). Adding brightfield to OCT gave no consistent benefit, reaching significance only for Random Forest (p = 0.026, power 0.62). A compact shared feature subset combined brightfield area dynamics with OCT texture, shape, and speckle-variance descriptors, all showing low repeat-scan variability relative to cohort variability. ConclusionsOCT radiomics provides a sensitive, reproducible, label-free high-throughput readout of spheroid radiation dose response that outperforms the current brightfield-based approach, without requiring concurrent brightfield acquisition. Key pointsO_LIOCT radiomics quantifies dose-dependent radiation response in 3D tumor spheroids. C_LIO_LIOCT-only models outperformed brightfield imaging in radiation dose prediction. C_LIO_LISelected radiomic features showed high repeatability across repeated acquisitions. C_LIO_LIAdding brightfield to OCT gave no consistent performance benefit. C_LIO_LILabel-free OCT enables reproducible, high-throughput spheroid radiation-response assessment. C_LI

cancer biology↗

bioRxiv2026

In situ vaccine effect of radiotherapy is associated with intratumoural ERV reactivation and RNA virus sensing

Radiotherapy (RT) transforms tumour tissues into in situ vaccines that trigger antitumor immunity. Immunogenicity depends on how RT is delivered, since heterogeneous RT (spatially fractionated RT, SFRT) elicits more prominent responses than the conventional homogenous one. However, this phenomenon cannot be clinically harnessed, unless the relevant pathways are identified. To gain insights, we developed a hybrid dry-lab/wet-lab approach that integrates systems-level immune phenotypes established by homogenous or heterogenous RT (SFRT) with the transcriptomic profiling of irradiated tumors. By further combining feature extraction with machine-learning, including multilayer perceptron modelling, we ranked predictors of immune infiltration and patient survivability for each RT type. We found that conventional RT induces coordinated upregulation of cytosolic sensors of RNA viruses (OASes and RIG I-like receptors) along with ERV RNAs predominately 400-800 base-pairs long, which might serve as their ligands. For schemes establishing abscopal effects, a coordinated upregulation of the OAS sensors and shared ERV transcripts was observed in both irradiated and distant tumours. Compared to homogenous RT, SFRT triggered earlier and stronger activation of OAS signaling along with NK cell responses. Overall, we show a co-involvement of tumour cell-intrinsic ERVs and their cytosolic RNA sensors in RT-induced antitumor immunity. This key finding could guide mechanistic studies and future precision oncology.

cancer biology↗

bioRxiv2025

Experimental investigation of oxygen diffusion in the peak and valley region of minibeam patterns during X-Ray irradiation

BackgroundMinibeam radiotherapy has demonstrated its potential to reduce normal tissue toxicity, while maintaining tumor control. However, the underlying mechanisms behind this phenomenon remain unknown. Recent theoretical studies suggest a dose surrogate by diffusion of H2O2 into the valley regions. PurposeThe aim of this study is to experimentally investigate oxygen depletion and diffusion upon minibeam (MB) irradiation. MethodsA 3D-printed water phantom with four sensors was developed to enable the real-time, simultaneous measurement of oxygen concentration in the peak and valley. Water with 0 % - 11 % O2 and 0.1 % / 5 % CO2 was irradiated with broad beam (BB) and MB characterized by peak and valley widths of 2 mm x 2 mm and 0.5 mm x 2 mm. The depletion was further compared in other chemical environments. ResultsThe oxygen depletion rates per dose in hypoxic water in the valley regions were found to be 3 to 7 times higher compared to the peaks or BB. This observation was found to be independent of oxygen concentration above 2 %, indicating oxygen depletion saturation. For MB, diffusion between peaks and valleys was observed. After a certain period, an equilibrium between diffusion and dose rate differences was established. Glutathione and HEPES as medium increased the depletion further and distinguished MB from BB. ConclusionsA novel way of simultaneously measuring oxygen in the peak and valley of the MB dose pattern was introduced. The observed oxygen depletion saturation and diffusion between the peaks and valleys suggest the importance of oxygen in spatially fractionated radiotherapy studies, which is even greater for 5 mM glutathione compared to water.

biochemistry↗

bioRxiv2022

Lipid Droplets Fuel Small Extracellular Vesicle Biogenesis

Despite an increasing gain of knowledge regarding small extracellular vesicle (sEV) composition and functions in cell-cell communication, the mechanism behind their biogenesis remains unclear. Here, we revealed for the first time that the sEV biogenesis and release into the microenvironment are tightly connected with another important organelle: Lipid Droplets (LD). We have observed this correlation using different human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results showed that the use of external stimuli such as radiation, pH, hypoxia, or lipid interfering drugs, known to affect the LD content, had a similar effect in terms of sEV secretion. Additional validations were brought using multiple omics data, at the mRNA and protein levels. Altogether, the possibility to fine-tune sEV biogenesis by targeting LDs, could have a massive impact on the amount, the cargos and the properties of those sEVs, paving the way for new clinical perspectives. Significance Statement

cancer biology↗

bioRxiv2021

Lipid Droplets and Ferritin Heavy Chain: a Devilish Liaison in Cancer Radioresistance

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological characteristic of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 restoration as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel molecular mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.

cancer biology↗

bioRxiv2017

Experience-induced forgetting by WT1 enables learning of sequential tasks.

Under physiological conditions, strength and persistence of memory must be regulated in order to produce behavioral flexibility. In fact, impairments in memory flexibility are associated with pathologies such as post-traumatic stress disorder or autism; however the underlying mechanisms that enable memory flexibility are still poorly understood. Here we identified the transcriptional repressor Wilms Tumor 1 (WT1) as a critical synaptic plasticity regulator that decreases memory strength, promoting memory flexibility. WT1 was activated in the hippocampus following induction of long-term potentiation (LTP) or learning. WT1 knockdown enhanced CA1 neuronal excitability, LTP and long-term memory whereas its over-expression weakened memory retention. Moreover, forebrain WT1-deficient mice showed deficits in both reversal, sequential learning tasks and contextual fear extinction, exhibiting impaired memory flexibility. We conclude that WT1 limits memory strength or promotes memory weakening, thus enabling memory flexibility, a process that is critical for learning from new experience.

neuroscience↗