This study aimed to investigate the spatial heterogeneity of molecular signature in the muscle of juvenile dermatomyositis (JDM) patients before and after treatment. Unsupervised reference-free deconvolution of spatial transcriptomics and standardized morphometry were performed in two JDM muscle biopsies with different clinical severity at disease onset and compared to healthy muscle. Identified signatures were scored in two additional JDM muscle biopsies from the same patient before and after remission. Disappearance of the normal muscle signature mostly corresponding to mitochondrial biology was observed in JDM. Three pathological transcriptomic signatures were isolated, related to “myofibrillar stress”, “muscle remodeling” and “interferon signaling” signatures. The “myofibrillar stress signature” was prominent in the most severe biopsy while the “muscle remodeling” signature was mostly present in the biopsy from the patient with good outcome. These signatures unveiled genes not previously associated with JDM including ANKRD1 and FSLT1 for “myofibrillar stress” and “muscle remodeling” signatures, respectively. Post-treatment analysis of muscle after two years remission showed a persistence of pathological signatures. This pilot study of JDM muscle identified spatially distributed pathological signatures that persist after remission. This work paves the way for a better understanding of the pathophysiology in affected muscle and the identification of biomarkers that predict relapse.

Recent evidence implicates altered RNA editing and dysregulated type I IFN signaling in immune-mediated diseases, including psoriasis, although the underlying genetic mechanisms remain poorly defined. We investigated four unrelated multiplex families with early-onset plaque psoriasis, with or without psoriatic arthritis, segregating as a monogenic trait and characterized by a strong IFN signature in skin and blood. Whole-exome sequencing identified four rare heterozygous loss-of-function mutations in ADAR1 cosegregating with disease and elevated IFN-stimulated gene expression. Six additional rare variants were detected in an independent cohort of 125 psoriasis patients. Single-cell transcriptomics identified keratinocytes and melanocytes as major IFN sources. Functional studies showed that ADAR1 knockdown or expression of ADAR1G1119R and ADAR1P3A alleles pathogenic variants reduced adenosine-to-inosine RNA editing and increased IFN-stimulated genes and inflammatory cytokines, effects reversed by upadacitinib and deucravacitinib. These findings define a novel IFN-dependent psoriasis subtype caused by inborn defects of ADAR1-mediated RNA editing, with direct implications for precision medicine in psoriatic disease.

Since the 1990s, the Pacific oyster ( Magallana gigas ) has experienced repeated mortality events associated with Ostreid herpesvirus 1 (OsHV-1). Although the virus has been genomically characterised, its replication cycle and its interactions with the oyster immune system are still not well understood. In particular, little is known about the dynamics of OsHV-1 gene expression and the immune responses of haemocytes from oysters with varying susceptibility to the virus. While some studies have focused on the expression of specific viral and host genes in whole oysters, none have provided a comprehensive analysis of genome-wide expression across multiple post-infection time points in haemocytes. The lack of oyster cell lines makes studying virus–host interactions in vitro challenging. However, haemocytes, the key immune cells circulating in haemolymph, can be maintained in vitro in the short term and represent a relevant model for analysing infection dynamics. In this study, haemocytes from two M. gigas batches, one highly susceptible and one less susceptible to OsHV-1, were infected in vitro . We tracked the viral and host transcriptomes over a 24-h period post-infection using high-throughput dual transcriptomics. Our results provide a detailed overview of the OsHV-1 transcriptomic landscape in haemocytes from high- and low-susceptible M. gigas over time. In addition, weighted correlation network analysis of host gene expression provided insights into the haemocytes’ response to infection and highlighted batch-specific immune responses. This comprehensive transcriptomic study is the first to describe virus–host interactions across multiple stages of infection in haemocytes from Pacific oysters, showing contrasted survival when exposed to OsHV-1.

BioStudies – one package for all the data supporting a study

Vers un atlas des micro algues vertes (Chlorophyta) dans l'océan: La lignée verte (i.e. les plantes) est représentée dans l'océan par les algues appartenant aux Chlorophyta. Celles-ci contribuent en moyenne à 25% des séquences photosynthétiques (Dinoflagellés exclus) retrouvées dans les inventaires moléculaires pan-océanique. Bien que les Chlorophyta jouent un rôle important dans l'écologie de l'océan et nous permettent de comprendre l'histoire évolutive des plantes terrestres, leur diversité et leur distribution dans les eaux marines du globe est peu documentée. Après avoir optimisé une base de données de séquences de références ARNr 18S, j'ai procédé à l'analyse de données de métabarcodes produits par Ocean Sampling Day (OSD), qui a fourni des données utilisant 2 régions hypervariables du gène du 18S appelées V4 et le V9. La comparaison des images de diversité produites par le V4 et le V9 a illustré l'influence de la base de référence sur la diversité. Ensuite, l'analyse de l'ensemble des V4 a permis d'étudier la distribution des Chlorophyta dans l'océan mondial. De plus, la vérification de l'assignation automatique des OTUs par reconstruction phylogénétique grâce à la base de référence produite en début de thèse, a permis de confirmer l'existence de nouvelles lignées de prasinophytes et de confirmer que la classe des Mamiellophyceae dominait les eaux côtières, alors que les clades VII et IX des prasinophytes dominaient les eaux océaniques oligotrophiques. Ces analyses ont aussi permis de montrer l'écart entre la diversité environnementale et celle dans la base de référence, en particulier pour les genres Ostreococcus et Micromonas (Mamiellophyceae).

BioStudies – one package for all the data supporting a study