Biology subjects

Toigo, M.

Publications and source records attributed to Toigo, M..

5 recordsLinked to original sources

bioRxiv2026

Epigenetic de-repression of basal cell metaplasia in aging AT2 cells is a risk factor for idiopathic pulmonary fibrosis (IPF).

Idiopathic pulmonary fibrosis (IPF) is a fatal, age-associated lung disease in which alveolar type II (AT2) cells lose regenerative capacity and can adopt aberrant basal-like fates that promote fibrosis. Using 3D organoid co-cultures with primary human fibroblasts, we find that healthy human AT2 cell trans-differentiation into KRT5+/KRT17+ basal cells increases progressively with age, while differentiation into RAGE+ AT1-like cells decreases. We identify a shared gene signature in AT2 cells at downstream targets of p63 characterized both by acquisition of bivalent, poised chromatin marks with age and increased accessibility in IPF, indicating epigenetic "priming" towards a basal cell lineage. In vitro treatment of young AT2 cells with IL-1{beta} recapitulates this priming toward basal differentiation via a NF-kB-regulated histone demethylase, JMJD3. Conversion of primed AT2 cells to a basal fate requires recruitment of a shared transcription factor, KLF5, from AT1-specific to basal-specific promoters by HIF-1. AT2 cells instead convert to KRT5-/KRT17+ basaloid cells via a non-age-dependent pathway that requires KLF5-SMAD2/3 complexing through TGF{beta}1 signaling. These findings define an inflammation-driven epigenetic de-repressive mechanism that links aging, inflammatory stress, hypoxia, and dysfunctional epithelial metaplasia, and accounts for the likely origin of aberrant epithelial cell populations in fibrotic lung disease.

cell biology↗

bioRxiv2026

Loss of competitive strength in European conifer species under climate change

Climate change is expected to alter species assemblages by affecting the outcome of competition between species. Investigating processes of competition remains challenging particularly in tree communities, as they unfold over extensive spatio-temporal scales. Here, we developed a deep-learning approach to leverage a novel database of 135 million simulated local-scale tree responses to climate across continental Europe to investigate changes in the competitiveness of nine major tree species under different scenarios of climate change. Specifically, we trained a Deep Neural Network on local process model projections to investigate climate change effects on indicators of competitive strength and species dominance. We found decreasing competitive strength for all investigated evergreen coniferous species across their distribution, while major deciduous broadleaved species such as Quercus robur and Fagus sylvatica increased in competitiveness. Changes in tree species competition with climate differed locally, but most investigated species lost competitive strength at their warm range edges. As a consequence of these changes, up to 19% of Europes forests could experience a change in the dominant tree species until the end of the 21st century. Our results suggest a profound climate-induced reassembly of Europes forests and identify areas that may require specific attention in forest policy and management.

ecology↗

bioRxiv2025

Alveolar Type II Cell-derived MMP1high basal cells promote destructive microcysts in idiopathic pulmonary fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease characterized by progressive epithelial metaplasia and widespread fibrosis. Alveolar microcysts develop near terminal airways in IPF and are linked to poor outcome. Using HTII-280 as a short-term lineage marker of AT2-derived AT0 (SFTPC+/SCGB3A2+) and basaloid (KRT17) cells, together with organoids and spatial transcriptomics (Xenium), we highlight epithelial similarities between respiratory bronchioles (RBs) and alveolar microcysts both having AT0, SCGB3A2+, and basaloid/basal cells (BCs), albeit with expanded BCs in IPF microcysts. The AT0- and AT2-derived BCs strongly express the collagenase, matrix metalloproteinase protein-1, MMP1 in organoids -- mirroring in situ BCs lining IPF microcysts, but distinct from MMP1low BCs in large airways or normal lungs. Expression of MMP1 correlates with basal cell hypoxia pathway activity. MMP1high AT2-derived BCs and IPF BCs promoted type 1 collagen degradation ex vivo and in vivo after xenotransplantation, forming microcystic structures that were abrogated by concurrent MMP inhibitor treatment. Notably, a Frizzled 5 WNT agonist antibody reversed the MMP1high state of AT2-derived BCs, raising a possible therapeutic approach. These findings suggest AT2 transdifferentiation to basaloid/basal cells is uncommon in normal lungs but can expand as a potential source of alveolar destruction, likely contributing to the pernicious course of IPF.

cell biology↗

bioRxiv2025

Targeting p16INK4a reverses alveolar epithelial cell dysfunction and induces lung regeneration in emphysema

Pulmonary emphysema involves impaired regenerative capacity of alveolar type 2 epithelial cells (AT2), the main progenitor cells in alveoli. However, the mechanisms underlying dysfunctional epithelial repair remain unclear. In a mouse model of elastase-induced emphysema, we observed an accumulation of activated AT2s in the lung, associated with an overexpression of p16INK4a (p16), a cell cycle inhibitor known to influence stem cell fate. Deletion of p16 promoted the transition of AT2 into alveolar type 1 (AT1) cells, resulting in tissue regeneration in both mice and alveolar organoids. Pharmacological targeting of the p16 pathway using senolytic agents recapitulate this regenerative effect, further supporting the role of p16 as a key brake on epithelial plasticity. These findings demonstrate that alveolar epithelial cell dysfunction can be reversed by p16 deletion or by eliminating p16+ cells, thereby reactivating the AT2-to-AT1 transition and promoting endogenous alveolar regeneration. This work identifies the p16 pathway as a promising therapeutic target for restoring damaged alveoli in emphysema.

cell biology↗

bioRxiv2021

Tree diversity effects on forest productivity: disentangling the effects of tree species addition vs. substitution

O_LIMixture effect on stand productivity is usually apprehended through a substitutive approach, whereby productivity in mixed stands is compared to productivity in monocultures, at equivalent stand density. This approach has proved that in many cases mixed stands perform better than monospecific forests, however, we do not yet have a solid theory about species behaviour in the mixture or even guidelines for combining species. The addition of a second tree species to an existing mono-specific stand has received much less consideration. Yet, this approach has the potential to separate the facilitation effect from the complementarity effect. C_LIO_LIWe compared the effect of tree species substitution vs. addition on the productivity of maritime pine and silver birch in a young tree diversity experiment implemented in 2008 in SW France. C_LIO_LISubstituting pines with birches to create two-species mixtures resulted in an increase of tree productivity at stand level beyond what was expected from monocultures (i.e., overyielding). In contrast, creating mixture through the addition of birches to pine stands had no effect on the maritime pine stand productivity (transgressive mixture effect not significant). This absence of effect is produced by two distinct density-dependence responses at an individual level. C_LIO_LIOur results allow clarifying the cases in which a mixed stand can be considered as an alternative to a monoculture of a productive species. In particular, the addition of a pioneer and soil low-demanding species during young developmental stages is a possibility to diversify the stand and potentially to increase ecosystem services without altering the productivity of the target species. C_LI

ecology↗