Biology subjects

Gidrol, X.

Publications and source records attributed to Gidrol, X..

7 recordsLinked to original sources

bioRxiv2026

Space partitioning by self-organized epithelial networks

Branching epithelia build supracellular networks that must simultaneously ensure connectivity, mechanical integrity, and efficient space partitioning, yet a general framework for how such networks form beyond the endothelial lineage has been lacking. Here we show that epithelial cells from multiple branching organs spontaneously self-organize into extended reticulate networks in simplified environments, revealing a conserved network-forming capacity. Combining wide-field lensless holographic imaging, deep-learning segmentation (EpiNet), and graph-theoretic analysis, we resolve a reproducible assembly sequence - contact initiation, clustering, percolation, and post-percolation relaxation - and quantify its geometry across scales. Actomyosin contractility controls both the growth of connectivity and the relaxation dynamics that set network geometry, tuning the effective cost of forming connections and thereby selecting between tree-like and reticulate topologies. After percolation, epithelial networks behave as active tension networks that progressively refine space partitioning toward centroidal, near-optimal configurations while maintaining a characteristic mesh size through continuous edge nucleation. These findings establish epithelial network formation as a generic, physically regulated mode of tissue self-organization and provide a quantitative framework linking single-cell mechanics, network topology, and space-partitioning dynamics, with implications for branching morphogenesis, organoid models, and tissue engineering.

biophysics↗

bioRxiv2026

Human decellularized extracellular matrix from adipose tissue is a permissive microenvironment for pancreatic organoids generation

In vitro reconstruction of human tissue microenvironments that integrate native biochemical and biomechanical cues is essential for disease modelling, regenerative medicine, and personalized therapeutic approaches. However, most currently available engineered matrices fail to recapitulate the complexity and tissue specificity of the human extracellular matrix (ECM). To address this limitation, we developed a novel hydrogel derived from decellularized human adipose tissue (atdECM) designed to support three-dimensional culture of human cells. The decellularization and delipidation processes were first validated, and the biochemical composition and biomechanical properties of atdECM were comprehensively characterized. Human pancreatic organoids were then cultured within atdECM hydrogel, and their structural organization and transcriptional profiles were analyzed and compared with those obtained in Matrigel, the current gold-standard matrix for organoid culture. Proteomic and cytokine analyses demonstrated efficient decellularization while preserving collagen-rich ECM architecture and a diverse repertoire of soluble bioactive factors. AtdECM exhibited physiological stiffness and retained tissue-specific extracellular cues. Pancreatic organoids cultured in atdECM displayed morphological similarities with those grown in Matrigel but exhibited transcriptional profiles more consistent with physiological epithelial homeostasis, with reduced activation of inflammatory and stress-related pathways. Altogether, these findings indicate that atdECM provides a human-derived, tissue-relevant, and permissive microenvironment for human organoid generation. This platform represents a promising alternative to Matrigel for studying human tissue biology and for developing physiologically relevant in vitro models.

bioengineering↗

bioRxiv2024

Fusion of blood vessel organoids with human pancreatic islets improves insulin response over time.

Pancreatic islet transplantation is a promising treatment strategy for type 1 diabetes, however there are still major challenges to overcome, including vascularization. Novel strategies for the generation of prevascularized islets with native microvessels have reported improved islet functionality, vascularization and engraftment emphasizing integral role of microvascular bed. Recently a new model of self-organizing three-dimensional human blood vessel organoids (BVOs) has been developed from human pluripotent stem cells (hPSCs), composed of both endothelial and mural cells. BVO recapitulate key features of human microvasculature such as formation of vascular network, vascular lumen and basement membrane, and have been shown to be perfusable. Here, we report a new strategy to construct prevascularized islets by fusion with hPSC-derived BVOs. We demonstrate that islets and BVOs in co-culture leads to fusion and improved insulin secretion over time, on two independent human islet donors, suggesting a new therapeutic approach for pancreatic islet transplantation and type 1 diabetes modeling.

bioengineering↗

bioRxiv2022

Detection of genes with differential expression dispersion unravels the role of autophagy in cancer progression

The majority of gene expression studies focus on the search for genes whose mean expression is different between two or more populations of samples in the so-called "differential expression analysis" approach. However, a difference in variance in gene expression may also be biologically and physiologically relevant. In the classical statistical model used to analyze RNA-sequencing (RNA-seq) data, the dispersion, which defines the variance, is only considered as a parameter to be estimated prior to identifying a difference in mean expression between conditions of interest. Here, we propose to evaluate two recent methods, MDSeq and DiPhiSeq, which detect differences in both the mean and dispersion in RNA-seq data. We thoroughly investigated the performance of these methods on simulated datasets and characterized parameter settings to reliably detect genes with a differential expression dispersion. We applied both methods to The Cancer Genome Atlas datasets. Interestingly, among the genes with an increased expression dispersion in tumors and without a change in mean expression, we identified some key cellular functions, most of which were related to catabolism and were overrepresented in most of the analyzed cancers. In particular, our results highlight autophagy, whose role in cancerogenesis is context-dependent, illustrating the potential of the differential dispersion approach to gain new insights into biological processes. Author summaryGene expression is the process by which genetic information is translated into functional molecules. Transcription is the first step of this process, consisting of synthesizing messenger RNAs. During recent decades, genome-wide transcriptional profiling technologies have made it possible to assess the expression levels of thousands of genes in parallel in a variety of biological contexts. In statistical analyses, the expression of a gene is estimated by counting sequencing reads over a set of samples and is defined by two dimensions: mean and variance. The overwhelming majority of gene expression studies focus on identifying genes whose mean expression significantly changes when comparing samples of different conditions of interest to gain knowledge of biological processes. In this classical approach, the variance is usually considered only as a noise parameter to be estimated before assessing the mean expression. However, finely estimating the variance of expression may be biologically relevant since a modification of this parameter may reflect a change in gene expression regulation. Here, we propose to evaluate the performance of statistical methods that identify such differentially variant genes. We highlighted the potential of this approach by analyzing cancer datasets, thus identifying key cellular functions in tumor progression.

bioinformatics↗

bioRxiv2021

An automated microfluidic platform integrating functional vascularized organoids-on-chip

The development of vascular networks on-chip is crucial for the long-term culture of three-dimensional cell aggregates such as organoids, spheroids, tumoroids, and tissue explants. Despite the rapid advancement of microvascular network systems and organoid technology, vascularizing organoids-on-chips remains a challenge in tissue engineering. Moreover, most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical settings to operate. Considering these constraints, we developed an innovative platform to establish and monitor the formation of endothelial networks around model spheroids of mesenchymal and endothelial cells as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 15 days on-chip. Importantly, these networks were functional, demonstrating intravascular perfusion within the spheroids or vascular organoids connected to neighbouring endothelial beds. This microphysiological system thus represents a viable organ-on-chip model to vascularize biological tissues and should allow to establish perfusion into organoids using advanced microfluidics.

bioengineering↗

bioRxiv2021

Microfluidic device integrating a network of hyper-elastic valves for automated glucose stimulation and insulin secretion collection from a single pancreatic islet

Advances in microphysiological systems have prompted the need for robust and reliable cell culture devices. While microfluidic technology has made significant progress, devices often lack user-friendliness and are not designed to be industrialized on a large scale. Pancreatic islets are often being studied using microfluidic platforms in which the monitoring of fluxes is generally very limited, especially because the integration of valves to direct the flow is difficult to achieve. Considering these constraints, we present a thermoplastic manufactured microfluidic chip with an automated control of fluxes for the stimulation and secretion collection of pancreatic islet. The islet was directed toward precise locations through passive hydrodynamic trapping and both dynamic glucose stimulation and insulin harvesting were done automatically via a network of large deformation valves, directing the reagents and the pancreatic islet toward different pathways. This device we developed enables monitoring of insulin secretion from a single islet and can be adapted for the study of a wide variety of biological tissues and secretomes.

bioengineering↗

bioRxiv2019

A New Ultradian Rhythm Linked to Protein Degradation and Synthesis in Mammalian Cells

We describe a new ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the individual histories of the dry mass of thousands of live cells simultaneously, each at a resolution of five minutes. Importantly, the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, has a period of 4 hours and is temperature-compensated. We demonstrated that the 4 hr rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents the periodic dynamics of protein mass in growing cells. Brief teaserWe have revealed a 4 hr rhythm in cell dry mass dynamics that seems to be general in proliferating mammalian cells.

cell biology↗