Biology subjects

Bosch, S.

Publications and source records attributed to Bosch, S..

6 recordsLinked to original sources

bioRxiv2026

Multi-omics profiling links epigenetic and lncRNA changes to early human endochondral ossification priming

Differentiation programs remain incompletely understood across stem cell types, including for human bone marrow mesenchymal stromal/stem (BM-MSCs) cells, a heterogenous population orchestrating bone formation and establishing a functional hematopoietic niche in the bone marrow. BM-MSCs form and repair bone through the evolutionarily conserved process of endochondral ossification (EO), initiated by deposition of a transient cartilage template subsequently remodeled into bone and bone marrow tissues. Despite their considerable potential for skeletal regeneration, the early molecular and cellular events underlying BM-MSCs commitment to EO remain elusive. To overcome donor dependent variability in chondrogenic potential that limits mechanistic studies, we here exploit OssiGel as a potent chondro-inductive extracellular matrix offering robust recapitulation of EO by BM-MSCs. Through multi-omics profiling of OssiGel-primed BM-MSCs, we identify rapid chromatin remodeling at chondrogenic loci as concomitant for lineage commitment. The emergence of a chondro-progenitor population is detected as early as 3 days in vivo and correlates with successful EO recapitulation. Mechanistically, we identify LINC02511 as novel enhancer-associated element involved in the onset of EO. We confirm presence of LINC02511 in human skeletal atlases, and its CRISPR-mediated silencing significantly impaired EO. By integrating human tissue engineering strategies with single cell multi-omics profiling, our study provides a framework for deciphering BM-MSCs fate decisions, highlighting the role of enhancer and non-coding elements as key determinants of early lineage specification. These findings advance our understanding of BM-MSCs biology and will prompt their translational exploitation in regenerative medicine.

cell biology↗

bioRxiv2026

Light-dependent cell fixing with DNA-targeting fluorophores

Light has become of paramount importance for the spatiotemporal control of cell labeling, activity and death. We found that palmatine, a DNA-binding alkaloid, mediates the fixation of live cells upon visible light irradiation. Fixation takes a few seconds or minutes depending on the power used, is accompanied by nuclear fluorescent labeling in target cells, exhibits a high degree of control from cell islets to single cells, yielding cells with intact nucleus and membrane boundaries. 'Optofixation' relies on palmatine-DNA interaction, singlet oxygen photogeneration and lipid peroxidation, producing fixing levels of endogenous aldehydes. We also establish that many commonly used nuclear dyes exhibit optofixation properties across the UV-far red spectrum. Comprising the straightforward inactivation and labeling of native target cells by small fluorophores, this unprecedented, comparatively simple technology has the potential for major applications in biological research.

cell biology↗

bioRxiv2024

Three-step scalable production of extracellular vesicles from pancreatic beta cells in stirred tank bioreactors promotes cell maturation and release of ectosomes with preserved immunomodulatory properties

Small extracellular vesicles (sEV) released by healthy beta cells are promising candidates for diabetes therapy thanks to their aptitude to modulate inflammation, to induce or maintain pancreatic function and to prevent pathogenic mechanisms. To advance the clinical development of therapeutics, there is a crucial need for scalable production methods. Stirred tank bioreactors (STR) are widely used in the industry due to their ability to provide homogeneous gas and nutrient supply, online monitoring, and efficient scale up. Anchorage- dependent cells can be cultured in STR on microcarriers or as spheroids, but may experience shear stress, which can affect sEV phenotype and function. Using pancreatic beta cells, this study identifies critical cell culturing parameters, including culture mode (monolayer vs. spheroids), medium formulation (with or without serum, glucose control), and process parameters (stirring, duration, cell density). The findings show that small spheroid culture promotes beta cell maturation without decreasing the yield of sEV per cell, despite a reduced cell surface exchange area. However, stirring increased expression of cellular stress markers and decreased cell viability. Set up of a three-step bioprocess allowed to maximize cell viability and sEV yields at high cell density over short production duration. sEV produced under these conditions maintained high purity, membrane integrity, and the aptitude to reduce T- lymphocyte proliferation and IFN-{gamma} cytokine secretion in a mixed lymphocyte reaction. Flow cytometry analysis revealed lower CD63/CD81 ratios in STR, indicating enhanced ectosome production. Switch from high glucose expansion to low glucose production medium further allowed to direct sorting of the antigen insulin into beta-sEV. This study demonstrates the feasibility of producing functional sEV from mature beta cells cultured as small spheroids, suitable for upscale. Production of sEV in STR may be particularly beneficial for ectosome- enriched compound loading for therapeutic applications. Graphical abstractRational development of a scalable bioprocess to control extracellular vesicles production & function. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/611247v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@6eaefeorg.highwire.dtl.DTLVardef@a2da3borg.highwire.dtl.DTLVardef@1a58f35org.highwire.dtl.DTLVardef@5cfd1d_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISmall 3D-spheroid culture promotes cell maturation C_LIO_LIStirring induces cellular stress responses & promotes ectosome release from the cytoplasmic membrane C_LIO_LIDesign of experiment efficiently enhances cell viability and EV yield with preserved immune-modulatory properties C_LIO_LIGlucose-starvation during the production phase directs insulin-sorting into extracellular vesicles C_LI

bioengineering↗

bioRxiv2023

Non-indigenous seaweeds in the Northeast Atlantic Ocean, the Mediterranean Sea and Macaronesia: a critical synthesis of diversity, spatial and temporal patterns

Effective monitoring and combatting the effect of non-indigenous seaweeds relies on a solid confirmation of the non-indigenous status of the species. We critically analysed the status of presumed non-indigenous seaweed species reported from the Mediterranean Sea, the Northeast Atlantic Ocean and Macaronesia, resulting in a list of 140 species whose non-indigenous nature is undisputed. For an additional 87 species it is unclear if they are native or non-indigenous (cryptogenic species) or their identity requires confirmation (data deficient species). We discuss the factors underlying both taxonomic and biogeographic uncertainties and outline recommendations to reduce uncertainty about the non-indigenous status of seaweeds. Our dataset consisted of over 19,000 distribution records, half of which can be attributed to only five species (Sargassum muticum, Bonnemaisonia hamifera, Asparagopsis armata, Caulerpa cylindracea and Colpomenia peregrina), while 56 species (40%) are recorded no more than once or twice. In addition, our analyses revealed considerable variation in the diversity of non-indigenous species between the geographic regions. The Eastern Mediterranean Sea is home to the largest fraction of non-indigenous seaweed species, the majority of which have a Red Sea or Indo-Pacific origin and have entered the Mediterranean Sea mostly via the Suez Canal. Non-indigenous seaweeds with native ranges situated in the Northwest Pacific make up a large fraction of the total in the Western Mediterranean Sea, Lusitania and Northern Europe, followed by non-indigenous species with a presumed Australasian origin. Uncertainty remains, however, regarding the native range of a substantial fraction of non-indigenous seaweeds in the study area. In so far as analyses of first detections can serve as a proxy for the introduction rate of non-indigenous seaweeds, these do not reveal a decrease in the introduction rate, indicating that the current measures and policies are insufficient to battle the introduction and spread of non-indigenous species in the study area. HighlightsO_LINon-indigenous seaweed species in the Northeast Atlantic Ocean, the Mediterranean Sea and Macaronesia are critically reanalysed. C_LIO_LI>19,000 distribution records revealed considerable variation in diversity of non-indigenous seaweed species in the study area. C_LIO_LITaxonomic and biogeographic uncertainties hamper a critical evaluation of the non-indigenous status of many seaweed species. C_LI

plant biology↗

bioRxiv2020

Molecular and functional diversity of distinct subpopulations of extracellular vesicles from stressed pancreatic beta cells: implications for autoimmunity

Beta cell failure and apoptosis following islet inflammation have been associated with autoimmune type 1 diabetes pathogenesis. As conveyors of biological active material, extracellular vesicles (EV) act as mediators in communication with immune effectors fostering the idea that EV from inflamed beta cells may contribute to autoimmunity. Evidence accumulates that beta exosomes promote diabetogenic responses, but relative contributions of larger vesicles as well as variations in the composition of the beta cells vesiculome due to environmental changes have not been explored yet. Here, we made side-by-side comparisons of the phenotype and function of apoptotic bodies (AB), microvesicles (MV) and small EV (sEV) isolated from an equal amount of MIN6 beta cells exposed to inflammatory, hypoxic or genotoxic stressors. Under normal conditions, large vesicles represent 93% of the volume, but only 2% of the number of the vesicles. Our data reveal a consistently higher release of AB and sEV and to a lesser extent of MV, exclusively under inflammatory conditions commensurate with a 4-fold increase in the total volume of the vesiculome and enhanced export of immune-stimulatory material including the autoantigen insulin, microRNA, and cytokines. Whilst inflammation does not change the concentration of insulin inside the EV, specific Toll-like receptor-binding microRNA sequences preferentially partition into sEV. Exposure to inflammatory stress engenders drastic increases in the expression of monocyte chemoattractant protein 1 in all EV and of interleukin-27 solely in AB suggesting selective sorting towards EV subspecies. Functional in vitro assays in mouse dendritic cells and macrophages reveal further differences in the aptitude of EV to modulate expression of cytokines and maturation markers. These findings highlight the different quantitative and qualitative imprints of environmental changes in subpopulations of beta EV that may contribute to the spread of inflammation and sustained immune cell recruitment at the inception of the (auto-) immune response. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/003145v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@1bf7c79org.highwire.dtl.DTLVardef@85098dorg.highwire.dtl.DTLVardef@362e33org.highwire.dtl.DTLVardef@11349ab_HPS_FORMAT_FIGEXP M_FIG C_FIG Inflammation stimulates release of a heterogeneous population of beta EV with differential expression of immunogenic substances involved in immune cell recruitment and activation. HighlightsO_LIStress engenders an up to four-fold increase in the volume of the vesiculome and enhanced auto-antigen release C_LIO_LICytokines are selectively sorted into EV subspecies C_LIO_LITLR-binding microRNAs are enriched in sEV C_LIO_LIEV from stressed beta cells promote dendritic and macrophage cell activation C_LI

immunology↗

bioRxiv2019

Population codes of prior knowledge learned through environmental regularities

How the brain makes correct inferences about its environment based on noisy and ambiguous observations, is one of the fundamental questions in Neuroscience. Prior knowledge about the probability with which certain events occur in the environment plays an important role in this process. Humans are able to incorporate such prior knowledge in an efficient, Bayes optimal, way in many situations, but it remains an open question how the brain acquires and represents this prior knowledge. The long time spans over which prior knowledge is acquired make it a challenging question to investigate experimentally. In order to guide future experiments with clear empirical predictions, we used a neural network model to learn two commonly used tasks in the experimental literature (i.e. orientation classification and orientation estimation) where the prior probability of observing a certain stimulus is manipulated. We show that a population of neurons learns to correctly represent and incorporate prior knowledge, by only receiving feedback about the accuracy of their inference from trial-to-trial and without any probabilistic feedback. We identify different factors that can influence the neural responses to unexpected or expected stimuli, and find a novel mechanism that changes the activation threshold of neurons, depending on the prior probability of the encoded stimulus. In a task where estimating the exact stimulus value is important, more likely stimuli also led to denser tuning curve distributions and narrower tuning curves, allocating computational resources such that information processing is enhanced for more likely stimuli. These results can explain several different experimental findings and clarify why some contradicting observations concerning the neural responses to expected versus unexpected stimuli have been reported and pose some clear and testable predictions about the neural representation of prior knowledge that can guide future experiments.

neuroscience↗