Biology subjects

Rocher, C.

Publications and source records attributed to Rocher, C..

8 recordsLinked to original sources

bioRxiv2024

Inositol-Requiring Enzyme 1 Pathway and Autophagy Drive Sequential Response of Endothelial Cells to Febrile Range Hyperthermia

ContextFever is an evolutionarily conserved and adaptive response during infections. However, prolonged fever has numerous systemic metabolic and functional side effects. In the heart, prolonged fever associated with infection is linked to fatal adverse effects, particularly involving impaired coronary circulation. Yet, the direct relationship between elevated temperature and coronary microcirculation dysfunction, remains to be fully demonstrated. In this study, we aimed to explore the specific responses of human coronary artery endothelial cells (HCAECs) to fever-range hyperthermia. MethodHCAECs were cultured at either 37{degrees}C or 40{degrees}C for up to 24 hours. Transcriptomic and proteomic profiles were obtained through microarray and mass spectrometry after 6, 12, and 24 hours of exposure. Key signaling pathways, upstream regulators, and candidate mechanisms were identified and validated at the mRNA and protein levels using mechanistic approaches. ResultsProlonged hyperthermia compromised HCAEC function, evidenced by cell detachment, loss of junctions, and increased permeability. HCAECs rapidly activated the unfolded protein response (UPR), including IRE1 activation and XBP1 splicing. Additionally, autophagic flux was significantly elevated, participating in the degradation of junction proteins. Pharmacological inhibition of IRE1 reduced the autophagic burden, protected against cell detachment, and preserved junction integrity over time. ConclusionOur findings reveal that in response to fever-range hyperthermia, the IRE1-autophagy axis regulates the survival and function of coronary endothelial cells. This mechanism could play a key role in modulating endothelial responses during infection and contribute to the pathological outcomes of fever. Furthermore, it may be relevant in local inflammatory conditions with elevated temperatures.

cell biology↗

bioRxiv2022

The compact genome of the sponge Oopsacas minuta (Hexactinellida) is lacking key metazoan core genes

BackgroundBilaterian animals today represent 99% of animal biodiversity. Elucidating how bilaterian hallmarks emerged is a central question of animal evo-devo and evolutionary genomics. Studies of non-bilaterian genomes have suggested that the ancestral animal already possessed a diversified developmental toolkit, including some pathways required for bilaterian body plans. Comparing genomes within the early branching metazoan Porifera phylum is key to identify which changes and innovations contributed to the successful transition towards bilaterians. ResultsHere, we report the first whole genome comprehensive analysis of a glass sponge, Oopsacas minuta, a member of the Hexactinellida. Studying this class of sponge is evolutionary relevant because it differs from the three other Porifera classes in terms of development, tissue organization, ecology and physiology. Although O. minuta does not exhibit drastic body simplifications, its genome is among the smallest animal genomes sequenced so far, surprisingly lacking several metazoan core genes (including Wnt and several key transcription factors). Our study also provided the complete genome of the symbiotic organism dominating the associated microbial community: a new Thaumarchaeota species. ConclusionsThe genome of the glass sponge O. minuta differs from all other available sponge genomes by its compactness and smaller number of predicted proteins. The unexpected losses of numerous genes considered as ancestral and pivotal for metazoan morphogenetic processes most likely reflect the peculiar syncytial organization in this group. Our work further documents the importance of convergence during animal evolution, with multiple emergences of sponge skeleton, electrical signaling and multiciliated cells.

evolutionary biology↗

bioRxiv2022

Multi-omics profiling of collagen-induced arthritis mouse model reveals early metabolic dysregulation via SIRT1 axis

Rheumatoid arthritis (RA) is characterized by joint infiltration of immune cells and synovial inflammation which leads to progressive disability. Current treatments improve the disease outcome, but the unmet medical need is still high. New discoveries over the last decade have revealed the major impact of cellular metabolism on immune cell functions. So far, a comprehensive understanding of metabolic changes during disease development, especially in the diseased microenvironment, is still limited. Therefore, we studied the longitudinal metabolic changes during the development of murine arthritis integrating metabolomics and bulk RNA-seq data. We identified an early change in macrophage pathways which was accompanied by oxidative stress, a drop in NAD+ level and induction of glucose transporters. We discovered inhibition of SIRT1, a NAD-dependent histone deacetylase and confirmed its dysregulation in human macrophages and synovial tissue of RA patients. Mining this database should enable the discovery of novel metabolic targets and therapy opportunities in RA.

cell 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

ASIGNTF: AGNOSTIC SIGNATURE USING NTF: A UNIVERSAL AGNOSTIC STRATEGY TO ESTIMATE CELL-TYPES ABUNDANCE FROM TRANSCRIPTOMIC DATASETS

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSMolecular signatures for deconvolution of immune cell types have been proposed, based on a methodology that relies on the biological classification of the cell types being studied. When working with less known biological material, a data-driven approach is needed to uncover the underlying classes and construct ad hoc signatures. ResultsWe introduce a new approach, ASigNTF: Agnostic Signature using Non-negative Tensor Factorization, to perform the deconvolution of cell types from transcriptomics data (RNAseq and microarray). ASigNTF, which is based on two complementary statistical/mathematical tools: non-negative tensor factorization (for dimensionality reduction) and the Herfindahl-Hirschman index (for signature selection), can be applied to any type of tissue as long as transcriptomic data on isolated cells is available. As a direct result of the new method, we propose two new signatures for the deconvolution of immune cell types, one consisting of a relatively small set of 415 genes, which is more compatible with microarray platforms, and a larger set of 915 genes. Using external datasets, our two signatures outperform the CIBERSORT LM22 signature in deconvolution of RNA-seq data. Our signature with 415 genes allows to recognize a larger number of cell types compared to the ABIS microarray signature. ConclusionsThe paper proposes a new method, ASigNTF; applies the method, and also provides a software implementation that allows to identify molecular signatures for deconvolution of complex tissues and specifically up to 16 immune cell types from micro-array or RNA-seq data. HO_SCPLOWIGHLIGHTSC_SCPLOWO_LISeveral signatures of immune cell types have been proposed, which follow a methodology deeply rooted in the known biological classification of the investigated cell types. C_LIO_LIWhen working with less known biological material, a more agnostic, data-driven approach is required to uncover the underlying classes and construct ad hoc signatures. C_LIO_LIWe present ASigNTF, a new agnostic approach to cell type classification and signature selection supported by an application software. C_LIO_LIWe discuss the results of benchmarking our proposed signatures, ABIS-seq and CIBERSORT on external datasets. C_LI

bioinformatics↗

bioRxiv2020

Beta and theta oscillations correlate with subjective time during musical improvisation in ecological and controlled settings: a single subject study

In this paper, we describe the results of a single subject study attempting at a better understanding of the subjective state during musical improvisation. In a first experiment, we setup an ecological paradigm measuring EEG on a musician in free improvised concerts with an audience, followed by retrospective rating of the mental state of the improviser. We introduce Subjective Temporal Resolution (STR), a retrospective rating assessing the instantaneous quantization of subjective timing of the improviser. We identified high and low STR states using Hidden Markov Models in two performances, and were able to decode those states using supervised learning on instantaneous EEG power spectrum, showing increases in theta and alpha power with high STR values. In a second experiment, we found an increase of theta and beta power when experimentally manipulating STR in a musical improvisation imagery experiment. These results are interpreted with respect to previous research on flow state in creativity, as well as with the temporal processing literature. We suggest that a component of the subjective state of musical improvisation may be reflected in an underlying mechanism related to the subjective quantization of time. We also demonstrate the feasibility of single case studies of musical improvisation using brain activity measurements and retrospective reports, by obtaining consistent results across multiple sessions.

neuroscience↗

bioRxiv2020

The buds of Oscarella lobularis (Porifera): a new convenient model for sponge cell and developmental biology

The comparative study of the four non-bilaterian phyla (Cnidaria, Placozoa, Ctenophora, Porifera) should provide insights into the origin of bilaterian traits. Except for Cnidaria, present knowledge on the cell biology and development of these animals is so far limited. Non-bilaterian models are needed to get further into cell architecture and molecular mechanisms. Given the developmental, histological, ecological and genomic differences between the four sponge classes, we develop a new sponge model: the buds of the Oscarella lobularis (class Homoscleromorpha). This experimental model supplements the two other most famous sponge models Amphimedon queenslandica and Ephydatia muelleri, both belonging to the class Demospongiae. Budding is a natural and spontaneous asexual reproduction mean, but budding can be triggered in vitro ensuring availability of biological material all year long. We provide a full description of buds, from their formation to their development into juveniles. Their transparency enables fluorescent and live imaging, and their abundance allows for experimental replicates. Moreover, regeneration and cell reaggregation capabilities provide interesting experimental morphogenetic contexts. The numerous techniques now mastered on these buds make it a new suitable sponge model. Summary statementStudying sponge biology is needed to understand the evolution of metazoans. We developed a new model suitable for experimental biology that allows to study morphogenetic processes with modern tools.

zoology↗

bioRxiv2020

A 3D human liver model of nonalcoholic steatohepatitis

AO_SCPLOWBSTRACTC_SCPLOWWe have developed an in vitro preclinical 3D Non-Alcoholic SteatoHepatitis (NASH) model by co-culturing four human primary liver cell types: hepatocytes, stellate, endothelial and Kupffer cells. Cells were embedded in a hydrogel of rat collagen in 96-well plate and a NASH-like environment was induced with a medium containing free fatty acids (FFAs) and tumor necrosis factor (TNF). This model was characterized by biochemical, imaging and transcriptomics analysis. On the one hand, we succeed in defining suitable culture conditions to maintain the 3D co-culture up to 10 days in vitro with the lowest level of steatosis, and reproducible low levels of inflammation and fibrosis. On the other hand, we induced NASH disease with a custom medium mimicking NASH features (hepatocyte injury, steatosis, inflammation and fibrosis). The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets. SO_SCPLOWUMMARYC_SCPLOWWe developed a 3D human liver model which exhibits many features of non-alcoholic steatohepatitis and that could become a platform for medium throughput drug screening.

cell biology↗