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Biology subjects

Piton, G.

Publications and source records attributed to Piton, G..

4 recordsLinked to original sources

Transplantation in neonate mouse recipients enhances umbilical cord blood CD34+ cells permissiveness to ETO2::GLIS2-driven transformation

Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive pediatric acute myeloid leukemia subtype, frequently driven by the ETO2::GLIS2 (EG) gene fusion in de novo AMKL patients. The EG fusion confers poor prognosis and high relapse risk. In a previous study, we demonstrated that human fetal hematopoietic cells are intrinsically permissive to EG-driven transformation and that microenvironmental cues critically enhance leukemogenesis in less permissive human cord blood (CB) cells. However, most pediatric AML models are established in adult recipient mice, potentially overlooking developmental niche-specific effects. Here, we investigated whether mouse neonates provide a more permissive environment for EG-driven leukemogenesis from human CB hematopoietic stem and progenitor cells (HSPCs). Comparison of xenotransplants of EG-transduced CB CD34+ cells into sublethally irradiated NSG neonate or adult mice show that neonatal recipients are more supportive of EG-driven leukemia when cell doses are adjusted for recipient size. Neonates exhibited a higher frequency of leukemia-initiating cells (LIC), enhanced expansion of EG/GFP+ leukemic cells, and increased disease penetrance compared with adults at similar dose/size ratio, despite similar overall human hematopoietic engraftment. Leukemic cells arising in neonates and adults displayed comparable phenotypes and secondary transplantation capacities, indicating functional equivalence. Both CD34+CD38- and CD34+CD38+ CB subpopulations were sensitive to EG-driven transformation, with neonates consistently showing higher LIC frequencies than adults. Together, our findings demonstrate that the developmental stage of the host microenvironment is a critical extrinsic determinant of EG-mediated leukemogenesis. Neonatal recipients constitute a physiologically relevant and highly sensitive model for studying pediatric AMKL initiation with low cell inputs, enabling refined investigation of microenvironmental signals that promote leukemia development and may reveal novel therapeutic vulnerabilities

cancer biology↗

The uptake of metallic nanoparticles in breast cancer cell lines is modulated by the HA-CD44 axis.

Radiation enhancement is a promising anti-cancer approach based on a local radiation dose increase due to the presence of metallic nanoparticles (NPs) within cancer cells. Depending on their composition, size and cellular properties, NPs can follow multiple cellular pathways and entry routes. We observed that gold, platinum and TiO2 NPs are internalized at higher levels in mesenchymal cells compared to epithelial cells in breast cancer models. A global survey of gene expression between epithelial and mesenchymal cells exposed to 4 different NP types revealed an involvement of membrane structure, and further experiments confirmed that the hyaluronic acid (HA) and its receptor CD44 are mediators of metallic NP uptake into cells. We extended our results to a larger panel of breast cancer cell lines and again showed a preferential uptake of all NPs tested in mesenchymal cells and relying on the HA/CD44 axis. These data provide considerations for the design of NP-based therapies targeting mesenchymal cancer cells, which are often resistant to treatment and correlate with poor prognosis and tumor recurrence.

cancer biology↗

Plants reverse the positive effect of nutrient addition on the drought resistance of soil multifunctionality

Increasing droughts threaten soil microbial communities and the multiple functions they control in agricultural soils. These soils are often fertilized with mineral nutrients, but it remains unclear how this fertilization may alter the capacity of soil multifunctionality (SMF) to be maintained under drought, and how plant-soil interactions shape these effects. In this study, we used a mountain grassland soil to test the interactive effect of mineral nutrient (Nitrogen and Phosphorous) addition and drought on SMF with and without plants (Lolium perenne) in a mesocosm experiment. We calculated SMF based on 8 microbial properties associated with the capacity of soil microbes to store carbon (C), nitrogen (N) and phosphorous (P) in their biomass, and to process these elements through organic matter depolymerization, mineralization, nitrification and denitrification processes. To investigate mechanisms underlying the SMF response we characterized the associated changes in soil stoichiometry and microbial community composition using 16S and 18S rRNA amplicon sequencing. Our results showed that fertilization decreased the SMF drought resistance when plants were present, but the opposite was observed in the unplanted mountain grassland soil. Our analysis suggested this was due to the interaction of plants, fertilization and drought in influencing four coupled properties related to high SMF: high soil moisture, low microbial C limitation, high bacterial diversity and low bacteria gram positive:gram negative ratio. Altogether, our results suggested that reducing the use of mineral fertilizer for plant production in mountain grassland could improve the ability of their soils to maintain their multifunctionality during drought period. Finally, our study clearly further demonstrated the importance of plant in the complex responses of SMF to global changes and showed that combining stoichiometric and microbial diversity assessment represents a powerful approach to disentangle the underlying mechanisms.

ecology↗

The contrasted impacts of grasshoppers on soil microbial activities in function of ecosystem productivity and herbivore diet

Herbivory can have contrasted impacts on soil microbes and nutrient cycling, which has stimulated the development of conceptual frameworks exploring the links between below- and aboveground processes. The "productivity model" predicts that herbivores stimulate microbial activities and accelerate nutrient mineralization in productive ecosystems, while they have an opposite effect in less productive ecosystems. In parallel, the "diet model" predicts that herbivores feeding on conservative plants accelerate nutrient cycling while those feeding on exploitative plants decelerate nutrient cycling, due to changes in litter inputs. Since these two frameworks can lead to conflicting predictions in some cases, experimental evidence combining herbivore diet and plant productivity is required. During two consecutive years, we conducted an experiment controlling the presence of three grasshopper species consuming either grasses, forbs or both in twelve natural and managed alpine grasslands with contrasted productivities. In order to assess the effects of herbivory on soil microbes, we measured their extracellular enzymatic activities, biomass and potential nitrogen mineralization (PNM). Soil and vegetation were also characterized to test how much they modulated the effects of herbivory on microbes. Contrary to the predictions of the diet model, the effects of herbivory on microbial characteristics did not depend on the herbivores diet, but were influenced by primary production, though in a way that differed from the productivity model. The most productive sites were constituted by exploitative plant species which depleted N resources in the soil, and by microbes producing relatively few extracellular enzymes, leading to a lower PNM. Herbivory increased microbial biomass and decreased the production of extracellular enzymes in those sites, possibly through the stimulation of root exudates produced by exploitative species. The least productive sites were characterized by conservative plants, high soil C content, and by microbes having a resource acquisition strategy (more extracellular enzymes, higher PNM). Herbivory decreased microbial biomass and increased the production of extracellular enzymes in those sites. This pattern can be explained by the loss of carbon associated with insect respiration, which increases the resource requirements of microbes and by a lower production of root exudates by conservative species. Therefore, the effects of two years of herbivory on soil microbes were at odds with the productivity model, which focuses instead on longer term effects corresponding to herbivory-induced changes in plant species composition. This highlights the multidimensional feature of the impacts of herbivory on ecosystem functioning, both in space and time.

ecology↗