Biology subjects

Carriere, M.

Publications and source records attributed to Carriere, M..

7 recordsLinked to original sources

bioRxiv2025

Effects of true to life polyethylene terephthalate and polycaprolactone nanoparticles on macrophages under a repeated exposure mode.

Micro and nanoplastics are pollutants which concentration in different biotopes increases continuously over time, which poses the question of their potential effects on health. In animals, these micro and nanoplastics are recognized as particulate materials and thus handled by macrophages, either directly in the case of lung exposure, or after the particles have crossed the epithelial barriers in case of oral or dermal exposure. It is thus important to study the potential effects of micro and nanoplastics on macrophages. Most studies have used an experimental scheme in which the cells of interest are exposed to a single dose of plastics, and where the readout of the studied parameters is made immediately after exposure. However, this classical experimental scheme does not take into account the impact of biopersistence, nor the potential cellular adaptation that may take place when cells are exposed repeatedly to a low dose of plastics. We thus used a repeated exposure scheme, in order to better take into account these phenomena. Within this frame, we compared the macrophages responses to a persistent nanoplastic, i.e. true-to-life polyethylene terephthalate nanoparticles and to a biodegradable nanoplastic, i.e. polycaprolactone, by a combination of proteomic and targeted experiments. Our results show that under this repeated exposure scheme, the proteome changes were of a lesser extent than under the acute exposure mode, indicating cell adaptation. However, polyethylene terephthalate nanoparticles induced oxidative stress and a pro-inflammatory response, while polycaprolactone nanoparticles induced a depression of macrophages functions, indicating harmful effects even in the repeated exposure scheme.

pharmacology and toxicology↗

bioRxiv2025

Enhancer Dynamics and Spatial Organization Drive Anatomically Restricted Cellular States in the Human Spinal Cord

Here, we report the spatial organization of RNA transcription and associated enhancer dynamics in the human spinal cord at single-cell and single-molecule resolution. We expand traditional multiomic measurements to reveal epigenetically poised and bivalent active transcriptional enhancer states that define cell type specification. Simultaneous detection of chromatin accessibility and histone modifications in spinal cord nuclei reveals previously unobserved cell-type specific cryptic enhancer activity, in which transcriptional activation is uncoupled from chromatin accessibility. Such cryptic enhancers define both stable cell type identity and transitions between cells undergoing differentiation. We also define glial cell gene regulatory networks that reorganize along the rostrocaudal axis, revealing anatomical differences in gene regulation. Finally, we identify the spatial organization of cells into distinct cellular organizations and address the functional significance of this observation in the context of paracrine signaling. We conclude that cellular diversity is best captured through the lens of enhancer state and intercellular interactions that drive transitions in cellular state. This study provides fundamental insights into the cellular organization of the healthy human spinal cord.

neuroscience↗

bioRxiv2024

Deleterious imprinting of perinatal exposure to nano-polystyrene on inflammatory bowel diseases

The tremendous and exponential production of plastics as well as its poor recycling leads to massive release in the environment questioning their outcomes on human health. Plastics are degraded into micro-plastic (MPL) and nano-plastic (NPL) that undergo weathering. MPL and NPL enter the human food chain via contaminated food, when animals are bred or vegetables grew on in plastic polluted environment and through the degradation of plastics food packaging. Ingested MPL or NPL can pass through epithelial barrier. This study focuses on consequences of oral perinatal exposure to polystyrene 50nm pristine or weathered (w) on intestinal disorders onset in offspring. Mouse were forced fed daily with 1.25mg of PS50 or PS50w starting at 15 days of gestation until pups weaned (Post Natal Day PND21). Oral tolerance protocol was induced at PND15 (nutritional switch) with ovalbumin (OVA) whereas DSS-induced colitis was performed in PND63 offspring. PS50 nor PS50w perinatal exposure did impair tolerance or immunization to OVA at PND15 in male or females. However, PS50 and PS50w perinatal exposure significantly worsened macroscopic score of DSS-induced colitis in both sexes. Perinatal exposure to PS50w appeared to be even more deleterious than PS50 for colitis exacerbation in males. In conclusion, early life exposure to PS50 or PS50w has long-lasting consequences on gut physiology by increasing the colonic severity of colitis while it does not modify oral tolerance establishment in early life. Those preliminary results questioned the kinetic of perinatal PS50 and PS50w exposure outcome over the life course and introduce the notion of imprinting. HighlightsO_LIPerinatal exposure to PS50 or PS50w does not affect oral tolerance establishment nor immune response to immunisation at PND15 C_LIO_LIPerinatal exposure to PS50 or PS50w have long lasting consequences on intestinal inflammation and colitis. PS50w in male has even more deleterious outcomes. C_LIO_LIRestricted exposure to PS50 or PS50w during perinatal has a deleterious imprinting on adult offspring intestinal health C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/629591v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@13bae52org.highwire.dtl.DTLVardef@131b42eorg.highwire.dtl.DTLVardef@2c7317org.highwire.dtl.DTLVardef@380df8_HPS_FORMAT_FIGEXP M_FIG C_FIG Environmental implicationThe use of plastics in daily products leads to ubiquitous contamination of the environment and subsequently of food chains. Plastics persist for long periods in the environment where, submitted to climate, they fragment into nanoplastic particles (NPL). Indeed, these NPL are weathered due to their exposure to UV light, thermal, chemical, physical and biological stresses. Thus, human populations are exposed to pristine (NPLp) and weathered NPL (NPLw) in their daily lives, with unknown effect on intestinal health, including the diseases development like adverse Food Reactions (AFR) or Inflammatory Bowel Diseases (IBD). Given that these pathologies could originate in perinatal development and that pregnant and breastfeeding women are exposed to NPL on a daily basis, this study explores the impact of perinatally exposure to pristine or weathered polystyrene nanoplastics on the gut development and susceptibility.

pathology↗

bioRxiv2024

Statistical estimation of sparsity and efficiency for molecular codes

AO_SCPLOWBSTRACTC_SCPLOWA fundamental biological question is to understand how cell types and functions are determined by genomic and proteomic coding. A basic form of this question is to ask if small families of genes or proteins code for cell types. For example, it has been shown that the collection of homeodomain proteins can uniquely delineate all 118 neuron classes in the nematode C. elegans. However, unique characterization is neither robust nor rare. Our goal in this paper is to develop a rigorous methodology to characterize molecular codes. We show that in fact for information-theoretic reasons almost any sufficiently large collection of genes is able to disambiguate cell types, and that this property is not robust to noise. To quantify the discriminative properties of a molecular codebook in a more refined way, we develop new statistics - partition cardinality and partition entropy - borrowing ideas from coding theory. We prove these are robust to data perturbations, and then apply these in the C. elegans example and in cancer. In the worm, we show that the homeodomain transcription factor family is distinguished by coding for cell types sparsely and efficiently compared to a control of randomly selected family of genes. Furthermore, the resolution of cell type identities defined using molecular features increases as the worm embryo develops. In cancer, we perform a pan-cancer study where we use our statistics to quantify interpatient tumor heterogeneity and we identify the chromosome containing the HLA family as sparsely and efficiently coding for melanoma.

bioinformatics↗

bioRxiv2023

Promoting intestinal healing by exclusive enteral nutrition with TGF-beta in a mouse model of colitis.

Background and aimsExclusive Enteral Nutrition (EEN) is the first line of treatment for pediatric Crohns disease (CD), but its mechanisms of action remain poorly understood. We studied EEN nutritional composition and TGF-{beta} effect in a mouse model of colitis, as well as the role of intestinal microbiota. MethodsMice were treated with Dextran Sulfate Sodium (DSS) during 5 days to induce colitis, until the inflammatory peak (day 7) or gut restitution (day 14). After DSS treatment, some of them received EEN formula such as Modulen IBD(R) (DM mice) or Infatrini Peptisorb(R) (DINF mice), with TGF-{beta} supplementation or neutralization, and clinical inflammation was evaluated. After sacrifice, macroscopic and microscopic inflammation were analyzed, as well as intestinal permeability (IP). The composition of mucosal colonic microbiota was analyzed and fecal microbiota transplantation was performed to evaluate its capacity to mediate anti-inflammatory and pro-regenerative effect. Colonic crypts from DSS and EEN mice were cultured as 3D organoids and cellular properties were analyzed. ResultsDSS mice developed colitis, as evidenced by the weight loss and clinical inflammation. It was accompanied by macroscopic inflammation such as colon thickness and edemas, and an elevated IP. In contrast, EEN mice with TGF-{beta} formula present faster weight recovery and decreased inflammatory parameters, with a normalized IP, suggesting gut restitution and functionality. These functional improvements were not obtained for EEN mice without TGF-{beta} formula. Moreover, EEN with Modulen IBD(R) (DM mice) modified the microbiota in comparison to DSS condition and attenuated inflammation. In addition, the organoids from DM mice colonic crypts treated had an enhanced survival, and re-epithelialization capacity. ConclusionsBoth EEN formula have anti-inflammatory properties, certainly by the nutritional composition. However, TGF-{beta} plays a significant role in intestinal restitution and restoring barrier function. These beneficial effects are partly mediated by the microbiota to maintain gut homeostasis.

physiology↗

bioRxiv2021

Immediate and sustained effects of cobalt-containing pigments on macrophages

Pigments are among the oldest nanoparticulate products known to mankind, and their use in tattoos is also very old. Nowadays, 25% of American people aged 18 to 50 are tattooed, which poses the question of the delayed effects of tattoos. In this article, we investigated three cobalt (Pigment Violet 14 (purple color)) or cobalt alloy pigments (Pigment Blue 28 (blue color), Pigment Green 14 (green color)), and one zinc pigment (Pigment White 4 (white color)) which constitute a wide range of colors found in tattoos. These pigments contain microparticles and a significant proportion of submicroparticles or nanoparticles (in either aggregate or free form). Because of the key role of macrophages in the scavenging of particulate materials, we tested the effects of cobalt- and zinc-based pigments on the J774A.1 macrophage cell line. In order to detect delayed effects, we compared two exposure schemes: acute exposure for 24 hours and an exposure for 24 hours followed by a 3-day post-exposure recovery period. The conjunction of these two schemes allowed for the investigation of the delayed or sustained effects of pigments. All pigments induced functional effects on macrophages, most of which were pigment-dependent. For example, Pigment Green 19, Pigment Blue 28, and Pigment White 4 showed a delayed alteration of the phagocytic capacity of cells. Moreover, all the pigments tested induced a slight but significant increase in tumor necrosis factor secretion. This effect, however, was transitory. Conversely, only Pigment Blue 28 induced both a short and sustained increase in interleukin 6 secretion. Results showed that in response to bacterial stimuli (LPS), the secretion of tumor necrosis factor and interleukin 6 declined after exposure to pigments followed by a recovery period. For chemoattractant cytokines (MCP-1 or MIP-1), delayed effects were observed with a secretion decreased in presence of Pigment Blue 28 and Pigment violet 14, both with or without LPS stimuli. The pigments also induced persisting changes in some important macrophage membrane markers such as CD11b, an integrin contributing to cell adhesion and immunological tolerance. In conclusion, the pigments induced functional disorders in macrophages, which, in some cases, persist long after exposure, even at non-toxic doses. Contribution to the field statementUnlike dyes, which are water-soluble, pigments are water-insoluble and thus viewed as inert coloring substances. However, historical pigments such as lead white or vermilion (mercuric sulfide) have been shown to be toxic, suggesting that pigments inertness may not be complete under biological conditions. Pigments being particulate (nano) materials, they are taken up by professional scavenger cells such as macrophages once they have penetrated into the body. One epitome of this situation is represented by tattooing: the pigments injected with the ink are taken up by dermal macrophages, which life cycle ensures the localized persistence of tattoos over time. Using an in vitro macrophage culture system adapted to study delayed effects, we have investigated the effects of a series of cobalt- and zinc-containing pigments on macrophages. First of all, the toxicity of the pigments correlated well with their solubility in acidic media, i.e. conditions prevailing in the phagolysosomes. Even when used at non-toxic doses, the cobalt and zinc pigments showed immediate and/or delayed effects on macrophage functions such as phagocytosis, adhesion, tissue repair or response to bacterial stimuli. Overall, these results show that some pigments may not be as inert as previously thought, and describe a system to investigate these effects.

immunology↗

bioRxiv2018

Topological Data Analysis of Single-cell Hi-C Contact Maps

In this article, we show how the recent statistical techniques developed in Topological Data Analysis for the Mapper algorithm can be extended and leveraged to formally define and statistically quantify the presence of topological structures coming from biological phenomena in datasets of CCC contact maps.

genomics↗