Biology subjects

Floris, E.

Publications and source records attributed to Floris, E..

4 recordsLinked to original sources

bioRxiv2026

Lung endothelial niche signaling governs self-renewal and fate transitions of human alveolar stem cells

Chronic lung diseases such as pulmonary fibrosis are characterized by the irreversible loss of alveolar type 1 (AT1) cells, yet the mechanisms governing human alveolar stem cell self-renewal and differentiation remain poorly defined. Here, we identify a lung endothelial niche that sustains the self-renewal of human alveolar type 2 (AT2) stem cells through MAPK signaling, enabling robust long-term expansion while preserving stem cell fate. Although YAP activation initiates AT1 transcriptional programs, it is insufficient to complete lineage maturation. We show that MAPK inhibition together with LATS inhibition promotes nuclear translocation of YAP, enhancing AT1 differentiation. Expanded human AT2 stem cells engraft in fibrotic lungs and contribute to alveolar regeneration while undergoing directed differentiation within diseased human lung tissue. Together, our findings define a niche-controlled signaling mechanism governing human alveolar stem cell fate and advance our understanding of alveolar regeneration.

cell biology↗

bioRxiv2025

A closed feedback between tissue phase transitions and morphogen gradients drives patterning dynamics

During development mechanochemical cues in the cell microenvironment are translated into signalling to drive cell fate decisions. As cells differentiate collectively, it raises the question of how tissue-level properties affect instructive cues of decision-making. Here, we show that a tissue rigidity phase transition guides patterning by tuning the length-scales and time-scales of morphogen signalling. By combining rigidity percolation theory, reaction-diffusion modelling, quantitative imaging, optogenetics and single-cell transcriptomics in zebrafish, we uncover dynamical global tissue rigidity patterns that actively shape the Nodal morphogen gradient by restricting ligand dispersal and accelerating its signalling activity. In this self-generated mechanism, Nodal, besides driving meso-endoderm fate specification, increases cell-cell adhesion strength via regulating planar cell polarity genes. Once adhesion strength reaches a critical point, it triggers a rigidity transition which collapses tissue porosity. The abrupt tissue reorganisation negatively feeds back on Nodal signalling impacting both its length-scales, by limiting Nodal diffusivity, and its time-scales, by speeding up the expression of its antagonist Lefty, thereby ensuring timely signal termination and robust patterning. Overall, we reveal how emergent properties set the spatiotemporal dynamics of morphogen gradients, uncovering macroscopic mechanisms of pattern formation.

developmental biology↗

bioRxiv2025

Adhesion-driven tissue rigidification triggers epithelial cell polarity

The active regulation of tissue material properties via phase transitions is central in morphogenesis. Transitions abruptly occur at critical points in diverse control parameters, including cell density, shape or adhesion. Whether these parameters are interdependent, performing redundant or distinct functions, is unknown. Here we show that co-regulation of multiple control parameters impacts not only tissue deformability, but also cell polarization. We theoretically define a new phase diagram capturing the material states of zebrafish pluripotent tissues and show that they cross simultaneously critical points in cell density, connectivity and adhesion strength. Combining optogenetics, biophysical measurements and quantitative morphometrics, we independently modulate each parameter, identifying adhesion as the main determinant of tissue rheology. Unexpectedly, uncoupling adhesion-driven from density-driven rigidification in amorphous tissues triggers epithelial organization via tricellular junction formation, followed by luminogenesis and apicobasal polarization. Altogether, this work reveals the non-linear dynamics of emergent tissue mechanics as instructive mechanisms of tissue organization.

biophysics↗

bioRxiv2022

Investigating the risk of cardiac fibrosis due to heat-not-burn cigarettes through human cardiac stromal cells

BackgroundThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. ObjectiveTo investigate the effects of circulating molecules in HNBC chronic smokers on the fibrotic specification and paracrine function of cardiac stromal cells (CSCs). MethodsResident CSCs were isolated from the atrial tissue of patients with cardiovascular diseases, and exposed to the serum of 60 young healthy subjects, stratified in exclusive HNBC smokers, traditional combustion cigarette (TCC) smokers, or non-smokers (NS) as reference. ResultsCSCs treated with TCC serum displayed impaired 3D growth and migration, as well as increased expression and/or release of pro-inflammatory and pro-fibrotic cytokines. Cells cultured with HNBC serum showed increased mRNA levels of pro-fibrotic genes, and reduced expression of the gap junction protein CX43. Nonetheless, both TCC and HNBC sera reduced the release of angiogenic and protective factors from CSCs. In fact, their paracrine support to tube-formation by endothelial cells and to preserved cell viability of cardiomyocytes in culture was significantly impaired. Treatment with the sera of both types of smokers also increased the expression of NOX isoforms and the release of H2O2 by CSCs. ConclusionThe circulating molecules in the serum of chronic HNBC smokers induce fibrotic specification in CSCs. They also reduce the beneficial paracrine effects of stromal cells on endothelial cells and cardiomyocytes, albeit to a reduced extent for some features. These results point to a potential risk for atrial fibrosis development triggered by chronic HNBC use. CONDENSED ABSTRACTThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. We isolated human stromal cells from the atrial tissue of patients with cardiovascular diseases, and exposed them to the serum of young healthy subjects, that are exclusive HNBC smokers. Results showed significant alterations in the phenotype of CSCs exposed to HNBC serum, suggesting a specification towards fibrosis, reduced support to parenchymal cells, and increased oxidative stress production. Data point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.

pathology↗