Biology subjects

Soler, C.

Publications and source records attributed to Soler, C..

5 recordsLinked to original sources

bioRxiv2024

TRESK background potassium channel in MrgprA3+ pruriceptors regulates acute and chronic itch.

TRESK (K2P18.1) is a background K+ channel expressed in sensory neurons, where it modulates the resting membrane potential, action potential firing and neuronal excitability. A subset of these sensory neurons, which express specific TRPs and Mas-related G protein-coupled receptors (Mrgprs), are activated by pruritogens and mediate itch sensations. Because TRESK is involved in somatosensation and pain transduction, we evaluated the contribution of this channel to pruritic sensitivity and its potential as a target for the treatment of chronic itch pathologies. By combining RNA in situ hybridization, calcium imaging, electrophysiological and behavioral approaches, we found that TRESK is involved in the modulation of non-histaminergic itch. TRESK is coexpressed with MrgprD+ and MrgprA3+ in sensory neurons and MrgprA3+ neurons from TRESK-/- animals display an enhanced firing compared to WT counterparts. Interestingly, acute itch to intradermal injection of chloroquine is significantly enhanced in the absence of TRESK but not the response to histamine, BAM8-22 or LTC4. TRESK deletion also enhanced chronic itch in mice models of Allergic Contact Dermatitis and Dry Skin. In the mouse model imiquimod-induced psoriasiform dermatitis, the absence of TRESK produced a significantly enhanced scratching behavior, which developed earlier and was more robust. Finally, enhancing TRESK function with the channel activator cloxyquin diminished both acute and chronic itch in WT mice but not in KO animals. In summary, our data indicates that TRESK is involved in regulating the excitability of a subset of sensory neurons that mediate histaminergic-independent itch. Enhancing the channel function with specific activators constitutes a novel anti-pruritic therapeutic method that can be combined with other compounds for the treatment of non-histaminergic itch, for which appropriate treatments are lacking.

neuroscience↗

bioRxiv2023

Amalgam plays a dual role in controlling the number of leg muscle progenitors and regulating their interactions with developing tendon

Formation of functional organs requires cell-cell communication between different cell lineages, and failure in this communication can result in severe developmental defects. Hundreds of possible interacting pairs of proteins are known, but identifying the interacting partners that ensure a specific interaction between two given cell types remains challenging. Here, we use the Drosophila leg model and our cell type-specific transcriptomic datasets to uncover the molecular mediators of cell-cell communication between tendon and muscle precursors. Through the analysis of gene expression signatures of appendicular muscle and tendon precursor cells, we identify two candidates for early interactions between these two cell populations: Amalgam (Ama) encoding a secreted protein and Neurotactin (Nrt) known to encode a membrane-bound protein. Developmental expression and function analyses reveal that: i) Ama is expressed in the leg myoblasts, whereas Nrt is expressed in adjacent tendon precursors, and ii) in Ama and Nrt mutants, myoblast-tendon cell-cell association is lost, leading to tendon developmental defects. Furthermore, we demonstrate that Ama acts downstream of the FGFR pathway to maintain the myoblast population by promoting cell survival and proliferation in a Nrt-independent manner. Together, our data pinpoint Ama and Nrt as molecular actors ensuring early reciprocal communication between leg muscle and tendon precursors, a prerequisite for the coordinated development of the appendicular musculoskeletal system.

developmental biology↗

bioRxiv2021

RNA-seq, bioinformatic identification of potential MicroRNA-Like Small RNAs in the edible mushroom Agaricus bisporus and experimental approach for their validation

Although genomes from many edible mushrooms are sequenced, studies on fungal miRNAs are scarce. Most of the bioinformatic tools are designed for plants or animals but fungal miRNAs processing and expression share similarities and differences with both kingdoms. Moreover, since mushroom species such as Agaricus bisporus (white button mushroom) are frequently consumed as food, controversial discussions are still evaluating whether their miRNAs might or might not be assimilated, perhaps within extracellular vesicles (i.e exosomes). Therefore, the A. bisporus RNA-seq was studied in order to identify potential de novo miRNA-like small RNAs (milRNAs) that might allow their later detection in the diet. Results pointed to 1 already known and 37 de novo milRNAss. Three milRNAss were selected for RT-qPCR experiments. Precursors and mature milRNAs were found in the edible parts (caps and stipes) validating the predictions carried out in silico. When their potential gene targets were investigated, results pointed that mostly were involved in primary and secondary metabolic regulation. However, when human transcriptome is used as target, the results suggest that they might interfere with important biological processes related with cancer, infectious process and neurodegenerative diseases.

bioinformatics↗

bioRxiv2019

Muscle MACF1 maintains myonuclei and mitochondria localization through microtubules to control muscle functionalities

Skeletal muscle is made from multinuclear myofiber, where myonuclei are positioned at the periphery or clustered below neuromuscular junctions (NMJs). While mispositioned myonuclei are the hallmark of numerous muscular diseases, the molecular machinery maintaining myonuclei positioning in mature muscle is still unknown. Here, we identified microtubule-associated protein MACF1 as an evolutionary conserved regulator of myonuclei positioning, in vitro and in vivo, controlling the \"microtubule code\" and stabilizing the microtubule dynamics during myofibers maturation, preferentially at NMJs. Specifically, MACF1 governs myonuclei motion, mitochondria positioning and structure and acetylcholine receptors (AChRs) clustering. Macf1-KO in young and adult mice decreases muscle excitability and causes evolutionary myonuclei positioning alterations in adult mice, paralleled with high mitochondria content and improved resistance to fatigue. We present MACF1 as a primary actor of the maintenance of synaptic myonuclei and AChRs clustering, peripheral myonuclei positioning and mitochondria organization through the control of microtubule network dynamics in muscle fibers.

cell biology↗

bioRxiv2017

Outbreak of invasive wound mucormycosis in a burn unit due to multiple strains of Mucor circinelloides f. circinelloides resolved by whole genome sequencing

Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole genome sequencing (WGS) analysis.\n\nWe analyzed M. circinelloides isolates from patients in our burn unit (BU1) together with non-outbreak isolates from burn unit 2 (BU2, Paris area) and from France over a two-year period (2013-2015). For each isolate, WGS and a de novo genome assembly was performed from read data extracted from the aligned contig sequences of the reference genome (1006PhL).\n\nA total of 21 isolates were sequenced including 14 isolates from six BU1 patients. Phylogenetic classification showed that the clinical isolates clustered in four highly divergent clades. Clade1 contained at least one of the strains from the six epidemiologically-linked BU1 patients. The clinical isolates seemed specific to each patient. Two patients were infected with more than two strains from different clades suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients shared one strain in BU1, suggesting direct transmission or contamination with the same environmental source.\n\nWGS coupled with precise epidemiological data and analysis of several isolates per patients revealed in our study a complex situation with both potential cross-transmission and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.\n\nImportanceInvasive wound mucormycosis (IWM) is a severe infection due to the environmental molds belonging to the order Mucorales. Severely burned patients are particularly at risk for IWM. Here, we used Whole Genome Sequencing (WGS) analysis to resolve an outbreak of IWM due to Mucor circinelloides that occurred in our hospital (BU1). We sequenced 21 clinical isolates, including 14 from BU1 and 7 unrelated isolates, and compared them to the reference genome (1006PhL). This analysis revealed that the outbreak was mainly due to multiple strains that seemed patient-specific, suggesting that the patients were more likely infected from a pool of diverse strains from the environment rather than from direct transmission between the patients. This study revealed the complexity of a Mucorales outbreak in the settings of IWM in burn patients, which has been highlighted based on whole genome sequencing and careful sampling.

microbiology↗