Biology subjects

Marchiano, F.

Publications and source records attributed to Marchiano, F..

6 recordsLinked to original sources

bioRxiv2022

The mitoXplorer 2.0 update: integrating and interpreting mitochondrial expression dynamics within a cellular context

Mitochondria are subcellular organelles present in almost all eukaryotic cells, which play a central role in cellular metabolism. Different tissues, health and age conditions are characterised by a difference in mitochondrial structure and composition. The visual data mining platform mitoXplorer 1.0 was developed to explore the expression dynamics of genes associated with mitochondrial functions that could help explain these differences. It however lacked functions aimed at integrating mitochondria in the cellular context and thus, identifying regulators that help mitochondria adapt to cellular needs. To fill this gap, we upgraded the mitoXplorer platform to version 2.0 (mitoXplorer 2.0). In this upgrade we implemented two novel integrative functions, Network Analysis and the transcription factor- (TF-) Enrichment, to specifically help identify signalling or transcriptional regulators of mitochondrial processes. In addition, we implemented several other novel functions to allow the platform to go beyond simple data visualisation, such as an enrichment function for mitochondrial processes, a function to explore time-series data, the possibility to compare datasets across species as well as an IDconverter to help facilitate data upload. We demonstrate the usefulness of these functions in 3 specific use cases. mitoXplorer 2.0 is freely available without login at http://mitoxplorer2.ibdm.univ-mrs.fr.

bioinformatics↗

bioRxiv2021

Tension-driven multi-scale self-organisation in human iPSC-derived muscle fibers

Human muscle is a hierarchically organised tissue with its contractile cells called myofibers packed into large myofiber bundles. Each myofiber contains periodic myofibrils built by hundreds of contractile sarcomeres that generate large mechanical forces. To better understand the mechanisms that coordinate human muscle morphogenesis from tissue to molecular scales, we adopted a simple in vitro system using induced pluripotent stem cell-derived human myogenic precursors. When grown on an unrestricted two-dimensional substrate, developing myofibers spontaneously align and self-organise into higher-order myofiber bundles, which grow and consolidate to stable sizes. Following a transcriptional boost of sarcomeric components, myofibrils assemble into chains of periodic sarcomeres that emerge across the entire myofiber. By directly probing tension we found that tension build-up precedes sarcomere assembly and increases within each assembling myofibril. Furthermore, we found that myofiber ends stably attach to other myofibers using integrin-based attachments and thus myofiber bundling coincides with stable myofiber bundle attachment in vitro. A failure in stable myofiber attachment results in a collapse of the myofibrils. Overall, our results strongly suggest that mechanical tension across sarcomeric components as well as between differentiating myofibers is key to coordinate the multi-scale self-organisation of muscle morphogenesis.

developmental biology↗

bioRxiv2021

Evolution of mechanisms controlling epithelial morphogenesis across animals: new insights from dissociation - reaggregation experiments in the sponge Oscarella lobularis.

BackgroundThe ancestral presence of epithelia in Metazoa is no longer debated. Even though Porifera seem to be the best candidates to be the sister group to all other Metazoa, hardly anything is known about the proteins involved in the composition of cell-cell junctions or about the mechanisms that regulate epithelial morphogenetic processes in this phylum. ResultsTo get insights into the early evolution of epithelial morphogenesis, we focused on morphogenic characteristics of the homoscleromorph sponge Oscarella lobularis. Homoscleromorpha are a sponge class with a typical basement membrane and adherens-like junctions unknown in other sponge classes. We took advantage of the dynamic context provided by cell dissociation-reaggregation experiments to explore morphogenetic processes in epithelial cells in an early lineage by combining fluorescent and electronic microscopy observations and RNA sequencing approaches at key time-points of the dissociation and reaggregation processes. ConclusionsOur results show that part of the molecular toolkit involved in the loss and restoration of epithelial features such as cell-cell and cell-matrix adhesion is conserved between Homoscleromorpha and Bilateria, suggesting their common role in the last common ancestor of animals. In addition, Sponge-specific genes are differently expressed during the dissociation and reaggregation processes, calling for future functional characterization of these genes.

evolutionary biology↗

bioRxiv2021

AnnoMiner: a new web-tool to integrate epigenetics, transcription factor occupancy, and transcriptomics data to predict transcriptional regulators

Gene expression regulation requires precise transcriptional programs, led by transcription factors in combination with epigenetic events. Recent advances in epigenomic and transcriptomic techniques provided insight into different gene regulation mechanisms. However, to date it remains challenging to understand how combinations of transcription factors together with epigenetic events control cell-type specific gene expression. We developed the AnnoMiner web-server and introduce an innovative and flexible way to annotate and integrate epigenetic, and transcription factor occupancy data. First, AnnoMiner annotates user-provided peaks with gene features. Second, AnnoMiner can integrate genome binding data from two different transcriptional regulators together with gene features. Third, AnnoMiner offers to explore the transcriptional deregulation of 10 genes nearby a user-provided peak. AnnoMiners fourth function performs transcription factor or histone mark enrichment analysis for user-provided gene lists by utilizing hundreds of public, high-quality datasets from ENCODE for the model organisms human, mouse, Drosophila and C. elegans. Thus, AnnoMiner can predict transcriptional regulators for a studied process without the strict need for chromatin data from the same process. We compared AnnoMiner to existing tools and experimentally validated several transcriptional regulators predicted by AnnoMiner to indeed contribute to muscle morphogenesis in Drosophila. AnnoMiner is freely available at http://chimborazo.ibdm.univ-mrs.fr/AnnoMiner/.

bioinformatics↗

bioRxiv2020

Prednisolone rescues Duchenne Muscular Dystrophy phenotypes in human pluripotent stem cells-derived skeletal muscle in vitro

Duchenne Muscular Dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced Pluripotent Stem Cells (iPSC) to a late myogenic stage. This allows to recapitulate classical DMD phenotypes (mislocalization of proteins of the Dystrophin-glycoprotein associated complex (DGC), increased fusion, myofiber branching, force contraction defects and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are due to anti-inflammatory properties. Our work introduces a new human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.

cell biology↗

bioRxiv2020

The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression

Skeletal muscles are composed of gigantic cells called muscle fibers, packed with force-producing myofibrils. During development the size of individual muscle fibers must dramatically enlarge to match with skeletal growth. How muscle growth is coordinated with growth of the contractile apparatus is not understood. Here, we use the large Drosophila flight muscles to mechanistically decipher how muscle fiber growth is controlled. We find that regulated activity of core members of the Hippo pathway is required to support flight muscle growth. Interestingly, we identify Dlg5 and Slmap as regulators of the STRIPAK phosphatase, which negatively regulates Hippo to enable post-mitotic muscle growth. Mechanistically, we show that the Hippo pathway controls timing and levels of sarcomeric gene expression during development and thus regulates the key components that physically mediate muscle growth. Since Dlg5, STRIPAK and the Hippo pathway are conserved a similar mechanism may contribute to muscle or cardiomyocyte growth in humans.

developmental biology↗