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Nava, M.

Publications and source records attributed to Nava, M..

3 recordsLinked to original sources

Integrin-identity shapes and mechanotemporally encodes the fibroblast transcriptome

Fibroblast transcriptomic states reflect physiological and pathological tissue contexts, yet the upstream determinants that stabilize these states remain poorly defined. Integrins mediate extracellular matrix (ECM) adhesion and biochemical signaling, but whether they encode mechanical constraints into stable transcriptomic programs is unclear. Using engineered mouse fibroblasts, bulk and single-cell transcriptomics, and controlled micromechanical confinement, we show that integrins can shape the transcriptomic landscape. The bulk transcriptome of fibroblasts expressing V- and {beta}1-class indicates a shared mechanosensitive baseline, except when these integrin classes are expressed individually. We also found integrin-specific gene clusters, including {beta}1-class integrin-dependent enrichment of Areg, Epha7, Lhpp and Igf2r, which regulate development, regeneration and disease, and altered YAP1 targeted gene expression. At single-cell resolution under confinement, {beta}1-class integrins sustain a progenitor-associated program, whereas their loss or V-class enrichment promotes a constitutively activated state linked to injury repair and wound healing. Mechanical confinement and confinement duration further reshapes these states in an integrin-identity-dependent manner. Our findings establish integrin-identity as a determinant of how fibroblasts transduce mechanotemporal inputs from the cell surface to the nucleus.

Cell Biology↗

Coupled nucleoplasmic flows and envelope expansion govern the mechanical resistance of the nucleus

In recent year, it became clear that the cell nucleus can undergo large deformations, during immune cell migration and tumor growth. These deformations generate signals that allow cells to sense their environment and adapt to it. How cells cope with and respond to large deformations thus strongly depends on the nuclear mechanics, but our understanding of the physical properties of the nucleus remains incomplete. In particular, it is not clear how the nuclear volume responds to deformation. Here we combine controlled confinement assays, high-resolution imaging and atomic force microscopy with theoretical modelling to propose a physical model of the cell nucleus that accounts for its surface and bulk properties and addresses both steady-state and transient regimes. Our results establish the nucleus as a poroelastic body in which mechanics are dominated by the envelope and dynamics by the chromatin, and suggest that regulating water permeability may be as important as softening the envelope for cells migrating rapidly through dense tissues.

biophysics↗

Multidimensional isotopic niches inform coexistence mechanisms in an Alpine ungulate community

O_LIUnderstanding functional community structure and the niche-based mechanisms that enable coexistence among sympatric species is essential for explaining how biodiversity is maintained in natural systems, and for anticipating how ecological communities will respond to ongoing environmental change. Stable isotope analysis provides a process-oriented perspective on resource use by integrating information across time and space, thereby allowing reconstruction of realised isotopic niches that reflect multiple dimensions of ecological differentiation. C_LIO_LIWe applied this framework to a community of ungulates in the Central-Eastern Italian Alps, including red deer (Cervus elaphus), roe deer (Capreolus capreolus), and Alpine chamois (Rupicapra rupicapra). Using stable isotope ratios in summer-grown hair segments ({delta}13C, {delta}15N, {delta}34S, {delta}18O, {delta}2H), we quantified species-specific n-dimensional niche hypervolumes within a Bayesian framework and estimated niche regions, overlap probabilities, univariate differentiation and multivariate structure. C_LIO_LIDespite broad dietary overlap typically observed among these ungulates, we found clear isotopic niche segregation, with mean pairwise overlap consistently remaining below 40%. Three dimensions emerged as primary drivers of differentiation: water sourcing ({delta}18O), diet quality ({delta}15N), and habitat openness ({delta}13C). Specifically, chamois appeared to derive more water from plants in their diet rather than from drinking, and to consume a higher-quality diet compared to Cervids. Red deer relied more heavily on forested habitats for resource use compared to roe deer and chamois, and additional isotopic differences between red deer and roe deer may stem from fine-scale abiotic conditions like microclimate and topography. We found no isotopic evidence for differential niche breadth among the three ungulate species. C_LIO_LITogether, these patterns highlight functional differentiation across multiple ecological axes, offering mechanistic insight into how these ungulates segregate realised niche space despite substantial potential for resource overlap. This multi-element isotope perspective underscores the value of integrative, process-based approaches for understanding current coexistence as well as improving predictions of how mammal communities may reorganise under accelerating environmental change. C_LI

ecology↗