Biology subjects

Blanc, M.

Publications and source records attributed to Blanc, M..

7 recordsLinked to original sources

bioRxiv2026

Autophagy deficiency in red pulp macrophages impairs their function and resistance to iron stress

In mammals, most of the iron is found in the heme of red blood cells (RBCs), which must be recycled to support erythropoiesis in the bone marrow. Splenic red pulp macrophages (RPMs) play a crucial role in this process by phagocytosing senescent RBCs, metabolizing the heme and releasing iron back into the blood. Free cytoplasmic iron generates toxic reactive oxygen species, yet iron-specific adaptations of RPMs are not well documented. We previously reported that autophagy prevents ferroptosis in Langerhans cells, a cutaneous phagocyte subset. Thus, we hypothesized that autophagy may be important for the regulation of RPM metabolism and their maintenance of systemic iron homeostasis. To study this, we used Atg5flox/flox and Cd169cre mouse models to delete ATG5 in CD169+ macrophages, including RPMs. Atg5-deficient RPMs were decreased in number, and the remaining ones showed increased generation of toxic lipid peroxides. Spleens of Atg5{Delta}Cd169 mice were enlarged and contained more RBCs. Finally, autophagy impairment in RPMs exacerbated RBC loss in a model of phenylhydrazine-induced anemia. Our findings exemplify how dysregulation of macrophage metabolism alters their function and can disrupt tissue homeostasis upon challenge.

immunology↗

bioRxiv2025

Multimodal cell lineage reconstruction in the hindbrain reveals a link between progenitor origin and activity patterning

Does the stem cell origin impact how daughter neurons acquire functional characteristics and assemble into circuits? Here, by multimodal cell lineage reconstruction in the zebrafish hindbrain we related a neurons embryonic origin to its future terminal differentiation features, such as neurotransmitter identity, and neuronal activity pattern. Intersectional lineage tracing, new developed computational tools, and genetic knockouts revealed that different progenitors formed functionally distinct neuron subtypes and could not compensate for the loss of adjacent progenitor pools, indicating developmental hardwiring. Dynamics of neuronal production suggest that progenitor competence changes over time. Whereas neurog1-expressing progenitors contributed to both glutamatergic and GABAergic lineages at early embryonic stages, later, other progenitor pools also assumed this role. Whole-hindbrain 3D atlases combining calcium imaging to monitor spontaneous neuronal activity, with genetic perturbations and progenitor origin information, unveiled that the emergence of neuronal activity patterns was presaged by their progenitor origins. This reveals a link between cell ontogeny and neuronal activity in the zebrafish hindbrain.

developmental biology↗

bioRxiv2025

A giant virus awakens virophage-like PLVs in the green alga Tetraselmis

Giant double-stranded DNA viruses profoundly influence algal population dynamics, yet their interactions with co-infecting mobile elements remain poorly understood. Here, we describe a natural tripartite infection system in the marine unicellular alga Tetraselmis striata, where a newly isolated giant virus, Oceanusvirus lionense (TetV-2), triggers the productive replication of multiple polinton-like viruses (PLVs). One PLV (Tsv-S2b) was co-isolated from the same seawater sample, while two others (Tsv-S2a and Tsv-S3b) derive from endogenous elements integrated in the algal genome. These PLVs depend strictly on TetV-2 for propagation and exert a virophage-like effect, reducing TetV-2 yields in a dose-dependent manner. Comparative genomics shows that virophagic PLVs retain a conserved structural module but harbor divergent replication and integration genes, supporting modular evolution of the PLV lineage. The reactivation of integrated PLVs mirrors the behavior of endogenous virophages in Cafeteria burkhardae, suggesting that specific Oceanusvirus-PLV compatibilities govern reactivation. This work provides direct evidence that integrated PLVs in green algae can transition to a virophage lifestyle upon infection by a giant virus, highlighting an inducible antiviral defense mechanism within photosynthetic protists. Author SummaryMarine microalgae are frequently infected by giant viruses, but how these infections are regulated is poorly understood. In the green alga Tetraselmis striata, we discovered that a giant virus can "wake up" small DNA viruses known as polinton-like viruses (PLVs) that are normally integrated and silent within the algal genome. Once activated, these PLVs multiply using the giant viruss replication machinery and, in turn, reduce its production. This helper-dependent relationship mirrors the behavior of virophages previously known only in non-photosynthetic protists. Our results reveal that microalgae possess an inducible antiviral system based on the reactivation of endogenous viral elements, suggesting that such interactions may be widespread in the oceans and play an important role in controlling algal virus epidemics.

microbiology↗

bioRxiv2023

A screening strategy based on two zebrafish eleuthero-embryo OECD test guidelines for the hazard assessment of chemicals: case of some bisphenol substitutes

The use of efficient screening strategies for the hazard assessment of chemicals is a current challenge to support regulatory requirements. Herein, we combined two eleuthero-embryo assays, a refined Fish Embryo Toxicity assay (OECD TG 236) and the EASZY assay (OECD TG 250), both using transgenic (tg) (cyp19a1b:GFP). The simultaneous performance of both assays provides complementary information about the acute toxicity, developmental effects, and estrogenic activity. A refined EASZY assay is however necessary to obtain accurate EC50. In this work we compared bisphenol A (BPA) and ten of its substitutes. In the refined FET, most of the selected bisphenols were more toxic than BPA, induced developmental effects on zebrafish embryos, some being identified as teratogenic compounds (BPF, BPS-MAE, BPC Cl, 4,4ODP), and ten of them induced GFP intensity. Endocrine activity of the BPs was further investigated in the EASZY assay at concentrations that do not affect the survival and the hatching rates or induce developmental toxicity based on the target concentrations used as previously defined in the refined FET. All bisphenols elicited an estrogenic activity with the notable exception of TCBPA. Most BPs were more estrogenic than BPA, acted as agonist ligands of zfER{beta}2 as shown in zebrafish-specific in vitro reporter gene assay and functional zfERs were required to induce brain aromatase. Interestingly, BPS-MAE and BPS-MPE behave as pro-estrogens as they were unable to transactivate zebrafish ER{beta}2 in vitro but induced brain aromatase in vivo. Overall, the implementation of the zebrafish eleuthero embryo-based screening strategy efficiently provided relevant data contributing to their environmental hazard. It also provides further evidence that bisphenols modulate cyp19a1b expression during early brain development whom potential short and long-term adverse effects need to be addressed. SYNOPSISa zebrafish eleuthero embryo-screening strategy based on OECD TGs was implemented for an efficient hazard assessment of bisphenols revealing that most of them are more toxic and/or estrogenic than BPA

pharmacology and toxicology↗

bioRxiv2022

Designed Ankyrin Repeat Proteins provide insights into the structure and function of CagI and are potent inhibitors of CagA translocation by the Helicobacter pylori type IV secretion system

The bacterial human pathogen Helicobacter pylori produces a type IV secretion system (cagT4SS) to inject the oncoprotein CagA into gastric cells. The cagT4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shaped N-terminal domains (CagIN) and prolonged by globular C-terminal domains (CagIC). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagIC with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagIC were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagIC plays a key role in cagT4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cagT4SS, a crucial risk factor for gastric cancer development. Author summaryHelicobacter pylori is a bacterial pathogen that colonises the human stomach in half of the worlds population. The most virulent strains use the cag- type IV secretion system (cagT4SS), a molecular nanomachine capable of injecting the oncoprotein CagA into gastric cells. How CagA is delivered is unknown, but the cagT4SS produces an external appendage referred to as pilus, which interacts with host cell receptors, mediating CagA translocation from the cytoplasm of the bacteria to the inner membrane of the host cell. In this study we have investigated the structural and functional properties of CagI, a protein long-thought to be associated with the cagT4SS pilus but with yet unknown function. We found that CagI displays a unique dimeric structure and that its C-terminal domain is involved in interaction with the host cell. Designed Ankyrin Repeat Proteins were selected against CagI and found to interact with its C-terminal moiety with high affinity. DARPin binding was able to prevent CagI interaction with the host cell and inhibited CagA translocation by H. pylori. Our study reveals the role of CagI in cagT4SS interaction with gastric cells and provides a first example of a small protein binder inhibiting the cagT4SS activity.

microbiology↗

bioRxiv2021

The 3D-atlas builder: a dynamic and expandable 3D-tool for monitoring the changes in the neuronal differentiation domain during hindbrain morphogenesis

Reconstruction of prototypic three-dimensional (3D) atlases at the scale of whole tissues or organs requires specific methods to be developed. We have established a digital 3D-atlas maker (DAMAKER) and built a digital 3D-temporal atlas to monitor the changes in the growth of the tissue and neuronal differentiation domain in the zebrafish hindbrain. DAMAKER integrates spatial and temporal data from cell populations, neuronal differentiation and brain morphogenesis, through in vivo imaging techniques paired with image analyses and segmentation tools. First, we generated a 3D-reference from several imaged hindbrains and segmented them using a trainable tool; these were aligned using rigid registration, revealing distribution of neuronal differentiation growth patterns along the axes. Second, we quantified the dynamic growth of the neuronal differentiation domain vs. the progenitor domain, and by in vivo neuronal birthdating experiments we generated a digital 3D-temporal map of the neuronal growth in the whole hindbrain, revealing the spatiotemporal dynamics of neuronal differentiation upon morphogenesis. Last, we applied it to glutamatergic and GABAergic neurons, as proof-of-concept that the digital 3D-temporal map could be used as a proxy to infer neuronal birthdate. As this protocol uses open-access tools and algorithms, it can be shared for standardized, accessible, tissue-wide cell population atlas construction.

developmental biology↗

bioRxiv2021

Survey data on European organic multi-species livestock farms

While there is increasing evidence of the sustainability benefits of diversified systems in the organic cropping sector, this has been much less investigated with organic livestock farming. To fill this knowledge gap, we surveyed a sample of 128 European organic multi-species livestock farms located across seven countries - Austria, Belgium, France, Germany, Italy, Sweden and Switzerland - and covering a large range of livestock species combinations. We recorded 1574 variables as raw data out of which we calculated 107 indicators describing farm structure, management and several sustainability dimensions: resource use efficiency and conservation, animal, land and work productivities, animal and human welfare. After technical validation of the data, we withdrew 26 farms and the database covers 102 farms. This database is well suited to unveil relationships between various dimensions of organic multi-species livestock farm sustainability and their structure and management. It can help reveal sustainable strategies for organic multi-species livestock farming systems and understand levers or barriers to their development.

ecology↗