Biology subjects

Morikka, J.

Publications and source records attributed to Morikka, J..

6 recordsLinked to original sources

bioRxiv2026

3D-Printable and Cytocompatible Hydrogel from Acinetobacter baylyi ADP1 Extracellular Matrix

Tissue engineering has advanced significantly, yet multicomponent hydrogels inspired by the compositional complexity of natural extracellular matrices (ECMs) are still underexplored. Most current hydrogels are based on single-component formulations, which can limit their biochemical and mechanical versatility. Developing synthetic multicomponent hydrogels remains challenging because it requires the controlled integration of multiple functional groups within a single material platform. Here, a biologically driven strategy is introduced by leveraging Acinetobacter baylyi ADP1, a bacterium that naturally produces extracellular polymeric substances (EPS) composed of a multicomponent matrix of polysaccharides and proteins. Through three-day cultivation and a simple extraction method, a hydrogel is obtained that can be methacrylated and photocrosslinked using red or blue light. This hydrogel is porous, cytocompatible, 3D-bioprintable, injectable, and undergoes rapid gelation for in situ crosslinking. This work highlights the potential of using bacterial-derived multicomponent hydrogels for biofabrication.

bioengineering↗

bioRxiv2025

OpTiles: An R Package for Adaptive Tiling and Methylation Variability Profiling

SummaryOpTiles is an R package that dynamically defines tiling windows based on the distribution of sequenced CpGs, addressing the limitations of traditional fixed-tiling approaches in targeted methylation datasets. By integrating CpG density with intra-region methylation variability, it provides a reliability metric and extended functionality for annotating, prioritizing, and interpreting complex methylation data. AvailabilityOpTiles is implemented in R and source code is freely available at https://github.com/fhaive/OpTiles. Data are available on Zenodo at https://doi.org/10.5281/zenodo.16961293 Contactdario.greco@tuni.fi

bioinformatics↗

bioRxiv2025

Alanine catabolism of Paneth cells maintains intestinal stem cell function during dietary restriction

Background and aimsPaneth cell niche promotes the function of intestinal stem cells (ISCs) during reduced food intake, but how ISC activity can be boosted when availability of resources is simultaneously reduced remains unknown. MethodsMice were subjected to dietary restriction (DR) and ad libitum (AL) dietary regime. FACS-sorted DR and AL Paneth cells and Lgr5+ stem cells were co-cultured, and organoid formation supportive capacity of Paneth cells was assessed. The role of Gpt2 - a Paneth cell specific mitochondrial alanine transaminase, was investigated by targeting pharmacologically and genetically in the intestinal organoids. By using U-13C labelled Alanine, an intercellular metabolic exchange assay was developed - and a conversion and transport of lactate from Paneth cells to stem cells, was followed by metabolomics. The in vivo role of Gpt2 was investigated in a conditional knock out mouse model. ResultsWe discovered that an increase in ISC function upon dietary restriction (DR) or DR mimicking condition, is dependent on Gpt2 in Paneth cells. Metabolic tracing of alanine directly showed DR boosts Paneth cell alanine catabolism, increasing lactate production via gluconeogenesis. Alanine derived lactate is shuttled from Paneth cells to neighboring stem cells, promoting TCA cycle and enhancing the ISC function during DR. Correspondingly, pharmacologic inhibition in vitro and genetic targeting of Gpt2 in vivo abolished the DR induced capacity of Paneth cells to support ISC function. ConclusionsOur results unravel dynamic intercellular metabolic cooperation in tissue adaptation, where Paneth cells upregulated Gpt2 catabolize increased amount of alanine to generate lactate as a transferable energy source, and to augment stem cell functions under DR.

cell biology↗

bioRxiv2024

Toxicogenomic Assessment of In Vitro Macrophages Exposed to Profibrotic Challenge.

Immune signalling is a crucial component in the progression of fibrosis. However, approaches for the safety assessment of potentially profibrotic substances, providing information on mechanistic immune responses, are underdeveloped. This study utilises a comprehensive analysis of RNA sequencing data from macrophages exposed in vitro to multiple sublethal concentrations of the profibrotic agent bleomycin, over multiple timepoints. Using a toxicogenomic framework, we performed dose-dependent analysis to filter genes truly altered by bleomycin exposure from noise and identified a subset of immune genes with a sustained dose-dependent and differential expression response to profibrotic challenge. We performed an immunoassay and revealed cytokines and proteinases responding to bleomycin exposure that closely correlate to transcriptomic alterations, underscoring the integration between transcriptional immune response and external immune signalling activity. This study not only increases our understanding of the immunological mechanisms of fibrosis, but also offers an innovative framework for the toxicological evaluation of substances with potential fibrogenic effects on macrophage signalling. Our work brings a new immunotoxicogenomic direction for hazard assessment of fibrotic compounds, through implementation of a time and resource efficient in vitro methodology.

pharmacology and toxicology↗

bioRxiv2022

Molecular annotation of AOPs guides the development of the next generation mechanistic chemical safety assessment and new approach methods

Mechanistic toxicology has emerged as a powerful framework to inform on the safety of chemicals and guide the development of new safe-by-design compounds. Although toxicogenomics provides support towards mechanistic evaluation of chemical exposures, the implementation of toxicogenomics-based evidence in the regulatory setting is still hindered by uncertainties related to the analysis and interpretation of such data. Adverse Outcome Pathways (AOPs) are multi-scale models that link chemical exposures to adverse outcomes through causal cascades of key events (KEs). The use of mechanistic evidence through the AOP framework is actively promoted for the development of new approach methods (NAMs) and to reduce animal experimentation. However, in order to unleash the full potential of AOPs and build confidence into toxicogenomics, robust and unified associations between KEs and patterns of molecular alteration need to be established. Here, we hypothesised that systematic curation of molecular events associated with KEs would enable the modelling of AOPs through gene-level data, creating the much-needed link between toxicogenomics and the systemic mechanisms depicted by the AOPs. This, in turn, introduces novel ways of benefitting from the AOP concept, including predictive models, read-across, and targeted assays, while also reducing the need for multiple testing strategies. Hence, we developed a multi-step strategy to annotate the AOPs relevant to human health risk assessment. We show that our framework successfully highlights relevant adverse outcomes for chemical exposures with strong in vitro and in vivo convergence, supporting chemical grouping and other data-driven approaches. Finally, we defined and experimentally validated a panel of robust AOP-derived in vitro biomarkers for pulmonary fibrosis.

pharmacology and toxicology↗

bioRxiv2021

LAM - an image analysis method for regionally defined organ-wide cellular phenotyping of the Drosophila midgut

Intestine is divided into functionally distinct regions along the anteroposterior (A/P) axis. How the regional identity influences the function of intestinal stem cells (ISCs) and their offspring remain largely unresolved. We introduce an imaging-based method, Linear Analysis of Midgut (LAM), which allows quantitative regionally defined cellular phenotyping of the whole Drosophila midgut. LAM transforms image-derived cellular data from three-dimensional midguts into a linearized representation, binning it into segments along the A/P axis. Through automated multi-variate determination of regional borders, LAM allows mapping and comparing cellular features and frequencies with subregional resolution. Through the use of LAM, we quantify the distributions of ISCs, enteroblasts and enteroendocrine cells in a steady state midgut, and reveal unprecedented regional heterogeneity in the ISC response to a Drosophila model of colitis. Taken together, LAM is a powerful tool for organ-wide quantitative analysis of the regional heterogeneity of midgut cells. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/427422v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@4083c0org.highwire.dtl.DTLVardef@189e297org.highwire.dtl.DTLVardef@17b577borg.highwire.dtl.DTLVardef@ac5013_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗