Biology subjects

Piastra-Facon, F.

Publications and source records attributed to Piastra-Facon, F..

3 recordsLinked to original sources

bioRxiv2025

Self-organization of tumor heterogeneity and plasticity

Phenotypic heterogeneity and plasticity drive tumor growth, metastasis, therapy resistance, and relapse. This heterogeneity is mainly interpreted as a response to external signals from the microenvironment. However, here we show that cancer cells also follow intrinsic self-organized programs that are sufficient to coordinate the spatiotemporal patterning of tumor cell states. By combining quantitative measurements in tumors and organoids with theoretical modeling, we reveal emergent mechanical gradients that orchestrate cell state transitions during colorectal tumor growth. Compression at the tumor center induces a transition from a fetal-like state into a cancer stem cell (CSC) state. The CSC compartment exhibits a characteristic size determined by tumor rheological properties. Once this size is surpassed, a translationally arrested apoptotic core emerges, triggering a shift from homogeneous proliferation to a hierarchical cell turnover. These findings uncover stereotyped programs of self-organization that likely cooperate with the microenvironment to shape tumor heterogeneity and plasticity.

cancer biology↗

bioRxiv2025

Macrophages restrict tumor permissiveness to immune infiltration by controlling local collagen topography through a Tcf4-Collagen3 fibrotic axis

During tumorigenesis, the extracellular matrix (ECM), which constitutes the structural scaffold of tissues, is profoundly remodeled. While the impact of such remodeling on tumor growth and invasion has been extensively investigated, much less is known on the consequences of ECM remodeling on tumor infiltration by immune cells. By combining tissue imaging and machine-learning, we here show that the localization of T lymphocytes and neutrophils, which orchestrate antitumor immune responses, can be predicted by defined topographical features of fibrillar collagen networks. We further show that these collagen topographies result from the activation of a fibrotic pathway controlled by the transcription factor Tcf4 upon depletion of tumor-associated macrophages at late tumor stages. This pathway promotes the deposition of collagen 3 by both tumor and stromal cells, resulting in intermingled collagen networks that favor intra-tumoral T cell and neutrophil localization. Importantly, analysis of human colorectal cancer public bulk RNAseq databases showed a strong correlation between Tcf4 and collagen 3, as well as between the expression of these genes and tumor infiltration by T lymphocytes and neutrophils, attesting the clinical relevance of our findings. This study highlights the key structural role of macrophages on the tumor extracellular matrix and identifies collagen network topographies as a major regulator of tumor infiltration by immune cells.

immunology↗

bioRxiv2020

The impact of genetic diversity on gene essentiality within the E. coli species

Bacteria from the same species can differ widely in their gene content. In E. coli, the set of genes shared by all strains, known as the core genome, represents about half the number of genes present in any strain. While recent advances in bacterial genomics have enabled to unravel genes required for fitness in various experimental conditions at the genome scale, most studies have focused on model strains. As a result, the impact of this genetic diversity on core processes of the bacterial cell largely remains to be investigated. Here, we developed a new CRISPR interference platform for high-throughput gene repression that is compatible with most E. coli isolates and closely-related species. We applied it to assess the importance of [~]3,400 nearly ubiquitous genes in 3 growth media in 18 representative E. coli strains spanning most common phylogroups and lifestyles of the species. Our screens highlighted extensive variations in gene essentiality between strains and conditions. Unlike variations in gene expression level, variations in gene essentiality do not recapitulate the strains phylogeny. Investigation of the genetic determinants for these variations highlighted the importance of epistatic interactions with mobile genetic elements. In particular, we showed how mobile genetic elements can trigger the essentiality of core genes that are usually nonessential. This study provides new insights into the evolvability of gene essentiality and argues for the importance of studying various isolates from the same species in bacterial genomics.

genomics↗