Biology subjects

Monaco, C.

Publications and source records attributed to Monaco, C..

7 recordsLinked to original sources

bioRxiv2026

Placental transcriptomics reveals alterations in metabolic and transport gene programs following prenatal cannabis smoke exposure

Background: Prenatal cannabis use is increasing, yet the effects of inhaled cannabis smoke on placental molecular function remain poorly defined. Objective: To characterize placental transcriptomic alterations following prenatal cannabis smoke exposure using a physiologically relevant murine inhalation model. Methods: Timed-pregnant CD-1 mice were exposed to cannabis cigarette smoke or room air from embryonic day (E)6.5 to 18.5. Placentae were collected at E18.5 for microarray-based transcriptomic profiling. Differential gene expression was assessed using fetal sex adjusted linear models and false discovery rate correction. Gene set variation and ranked pathway enrichment were performed to evaluate compartment-associated and biological transcriptional programs. Selected genes were validated by quantitative PCR. Results: Large-scale transcriptomic profiles revealed no clear visual clustering by exposure; however, 23 genes were differentially expressed (FDR <0.05, |log2 fold change| > 0.5). Labyrinth-associated transcriptional signatures were reduced, whereas junctional-associated signatures were increased in exposed placentae. Pathway analyses revealed negative enrichment of fatty acid metabolism, bioenergetic, and transmembrane transport pathways, alongside positive enrichment of RNA processing and transcriptional-regulatory pathways. Quantitative PCR confirmed altered expression of multiple transport-related genes. Electron transport chain-associated gene expression was altered despite preserved placental respiratory measurements. Conclusions: Prenatal cannabis smoke exposure is associated with subtle yet coordinated placental transcriptional alterations involving metabolic, transport-associated, and gene-regulatory pathways, alongside compartment-associated transcriptional shifts. These findings provide insight into placental responses to whole cannabis smoke exposure and identify pathways that may contribute to altered placental function during pregnancy.

physiology↗

bioRxiv2025

Innate antiviral readiness drives the expansion of protective T stem cell memory against influenza

The development of T-cell-based influenza vaccines relies on eliciting broad CD8+ T-cell immunity, wherein T stem cell-like memory (TSCM) cells serve as the ultimate long-lived reservoir for immune memory, thereby unlocking the potential for durable protection against viral drift and shift. However, the specific immunological cues that drive the robust expansion and functional preservation of this self-renewing, multipotent subset remain unknown. Here, utilizing multi-omic systems immunology in a pediatric cohort immunized with live attenuated influenza vaccine, we identified the determinants governing the expansion of influenza virus-reactive TSCM cells. We show that a pre-existing state of innate antiviral readiness, defined by a plasmacytoid dendritic cell-associated type I interferon signature, is the requisite condition for a robust TSCM expansion. Mechanistically, this baseline innate state enhances antigen priming and enforces a qualitative divergence in T-cell fate, driving responders toward a functionally poised, Th1-dominant phenotype while non-responders default to a dysfunctional, hyper-proliferative state. To determine the clinical relevance of this cellular subset, we analyzed an independent controlled human influenza challenge study. This validation revealed a critical functional division of labor in host defense: whereas pre-existing antibodies primarily mitigated symptom severity, the baseline frequency of influenza virus-reactive TSCM cells was the strongest predictor of rapid viral load clearance. These findings establish that the expansion of durable cellular memory is not stochastic but is predetermined by the innate cytokine environment, providing a predictive biomarker for patient stratification and a validated target for adjuvants designed to expand the TSCM reservoir deliberately.

immunology↗

bioRxiv2025

Prenatal cannabis smoke exposure alters placental development in a murine model of pregnancy

Cannabis use during pregnancy continues to increase with smoking remaining the most common mode of consumption. While clinical studies highlight an association between prenatal cannabis use and adverse pregnancy outcomes, less is known about placental outcomes, even though many of the reported pregnancy outcomes are thought to be mediated via placental dysfunction. Here, we established a mouse model of gestational cannabis smoke exposure to investigate the impacts on fetal outcomes and placental structure and function. Pregnant CD1 mice were exposed daily to {Delta}9-tetrahydrocannabinol (THC)-dominant cannabis smoke (12-14% THC, 0-2% CBD) or filtered air from embryonic day (E)6.5 to E18.5 or parturition. Cannabinoid analyses in cannabis smoke-exposed, paired maternal and fetal livers revealed total THC and 11-Nor-9-carboxy-THC (THCA) concentrations of 135.95 {+/-} 13.60 ng/g and 30.84 {+/-} 4.68 ng/g, respectively. Moreover, Cyp1a1, a smoke-inducible enzyme, was induced by 4-fold in cannabis smoke-exposed placentae. No changes in offspring body weights were observed; however, there was a marked decrease in the brain-to-body weight ratio of exposed postnatal day 1 (PND1) offspring. Placentae from exposed dams were significantly reduced in size, with altered zonation marked by a significantly decreased junctional zone and increased labyrinth zone. Key trophoblast differentiation markers (Tfap2c, Tpbpa, Pcdh12) and placental endocrine regulators (Pl2, Igf1r) were significantly downregulated following cannabis smoke exposure in placentas. Furthermore, transcript levels of placental nutrient and vascularization markers, Glut1, Vegfa and Pparg were significantly decreased in cannabis smoke-exposed placentas. By employing a physiologically relevant platform of prenatal cannabis exposure in vivo we demonstrate the adverse effects of prenatal cannabis smoke exposure on placental structure and function as well as on fetal brain growth.

physiology↗

bioRxiv2025

Divergent granulopoiesis at extramedullary sites safeguards host defense

Extramedullary organs such as the spleen can assume granulopoiesis as a supportive mechanism to cope with the demands during persistent inflammation. However, the quantitative output of extramedullary granulopoiesis is limited, thus raising the question if the spleen in fact provides neutrophils of a qualitative difference rather than merely contributing to neutrophil numbers. Here we report splenic stress granulopoiesis with distinct production and differentiation trajectories. Myeloid progenitors in the spleen engage in accelerated production of neutrophils with an immature phenotype. Yet, neutrophils generated during persistent stress granulopoiesis are fully competent to exert antimicrobial functions and are necessary to contain bacterial invasion. Activation of type I interferon signaling in the spleen is required for splenic neutrophil production and its loss impairs host defense. Thus, the spleen provides an immunological environment for stress-induced rapid production and priming of highly active neutrophils to meet the demands during infection.

immunology↗

bioRxiv2024

Exploring thermal tolerance across time and space in a tropical bivalve, Pinctada margaritifera

Ectotherms vulnerability to climate change is predicted to increase with temperature variations. Still, translating laboratory observations of organisms heat stress responses to the natural fluctuating environment remains challenging. In this study, we used an integrative framework combining insights from the TDT curves and physiological reaction norms, to precisely capture Pinctada margaritifera stage -specific thermal tolerance. On a second hand, this study aimed to explore applicability of the model of accumulation of thermal injury, by making in situ predictions at three contrasting sites across French Polynesia. By working with two life stages (early planktonic vs. spat), our study revealed an ontogenetic shift in lethal (CTmax) and sub-lethal (Tc) thermal limits, with higher vulnerability for early larval stages. Cumulative injury calculations resulted in thermal failure (100% injury) for larvae within 12 and 22 h, at the most extreme site (Nuku Hiva; T{degrees}C > 38{degrees}C), and warm lagoon (Reao Atoll), respectively. While substantial damages accumulated in spats, when exposed to consecutive extreme tides (Nuku Hiva) for 8 days. Overall, our results revealed that P. margarifiera is living closer to their upper thermal limits than previously estimated, and inhabit environments where important reduction of settlement and heat stress are already occurring during warmest months.

physiology↗

bioRxiv2024

The extracellular heparan sulfatase SULF2 limits myeloid IFNbeta signaling and Th17 responses in inflammatory arthritis.

Heparan sulfate (HS) proteoglycans are important regulators of cellular responses to soluble mediators such as chemokines, cytokines and growth factors. We profiled changes in expression of genes encoding HS core proteins, biosynthesis enzymes and modifiers during macrophage polarisation, and found that the most highly regulated gene was Sulf2, an extracellular HS 6-O-sulfatase that was markedly downregulated in response to pro-inflammatory stimuli. We then generated Sulf2+/- bone marrow chimeric mice and examined inflammatory responses in antigen-induced arthritis, as a model of rheumatoid arthritis. Resolution of inflammation was impaired in myeloid Sulf2+/- chimeras, with elevated joint swelling and increased abundance of pro-arthritic Th17 cells in synovial tissue. Transcriptomic and in vitro analyses indicated that Sulf2 deficiency increased type I interferon signaling in bone marrow-derived macrophages, leading to elevated expression of the Th17-inducing cytokine IL-6. This establishes that dynamic remodeling of HS by Sulf2 limits type I interferon signaling in macrophages, and so protects against Th17-driven pathology.

immunology↗

bioRxiv2020

Neuronal and synaptic plasticity in the visual thalamus in mouse models of glaucoma.

Homeostatic plasticity plays important roles in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes relate to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma - the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, but not younger D2 mice or microbead-injected mice. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in both ages of D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner in older D2 mice. Among D2 mice, functional changes observed in younger mice without elevated IOP were distinct from those observed in older mice with elevated IOP and RGC degeneration, suggesting that glaucoma-associated changes to neurons in the dLGN might represent a combination of stabilizing/homeostatic plasticity at earlier stages and pathological dysfunction at later stages.

neuroscience↗