Biology subjects

Hau, J.

Publications and source records attributed to Hau, J..

4 recordsLinked to original sources

bioRxiv2026

Decoding molecular programs that define macrophage responses to tumor-derived cues

Tumor-associated macrophages (TAMs) comprise functionally diverse states that can suppress anti-tumor immunity and promote tumor progression, yet the tumor microenvironmental cues and signaling programs that generate these states remain incompletely defined. Here, we systematically stimulate primary human monocyte-derived macrophages with a panel of cytokines and metabolites abundant in the tumor microenvironment (TME), and profile their transcriptomic and phosphoproteomic responses to resolve stimulus-specific molecular programs. We observe that potassium (K+) and adenosine (Ado) stimulation, which accumulate in necrotic tumor cores, downregulate antigen-presentation genes and their master regulator CIITA. K+ stimulation results in the upregulated fibronectin 1 expression, associated with immunosuppressive, metastasis-promoting TAM subsets. Ado induces upregulated expression of tryptophan (Trp) catabolism genes, myeloid checkpoints and metallothioneins (MTs). Although MT-high TAM states have been recurrently observed across tumor single cell RNA sequencing studies, their function remains poorly defined. We show that elevated MT expression in tumor tissue is associated with shorter overall survival. By aligning in vitro transcriptomes with single-cell RNA sequencing (scRNA-seq) signatures from a pan-cancer TAM atlas, we identify significant similarities between several in vitro states and clinically observed TAM populations, with Ado-stimulated macrophages closely resembling a MT-expressing TAM cluster. Overall, this work provides a systematic molecular context linking tumor microenvironmental cues to clinically relevant TAM states and offers a framework for recapitulating their functions in vitro. STATEMENT OF SIGNIFICANCEThis study explores how cytokines and metabolites from the tumor microenvironment shape macrophage molecular phenotypes and lead to the upregulation of clinically relevant marker genes and recapitulation of functional states of interest.

immunology↗

bioRxiv2025

Refining the adjuvant-induced rat model of monoarthritis by optimizing the induction volume and injection site

Arthritis is a highly prevalent and disabling condition characterized by pathological joint-damage, clinical symptoms of pain and loss of normal joint function. Monoarthritis can be modelled in rodents via intraarticular injection of complete Freund's Adjuvant (CFA), inducing both joint inflammation and pain-like behaviours. This study aimed to compare the outcome of different injection-volumes and joint-locations, to refine the model's use and to improve its validity. Male and female rats were injected with CFA into the ankle (10, 20 or 50 {micro}l) or knee (10, 50 or 100 {micro}l), and assessed on dynamic weight bearing, locomotor activity, depressive- and anxiety-like behaviours, histology, and a variety of welfare and model-specific parameters. Induction of monoarthritis resulted in relatively similar behavioural profiles regardless of the injected joint. The animals were highly affected in the acute phase, while less in the chronic phase. Greater volumes of CFA were associated with more profound behavioural changes and joint swelling. The largest volumes induced a pronounced local spread of inflammation to adjacent joints, which was reduced with intermediate volumes without attenuating the model validity. Reducing induction volumes to 20 and 50 {micro}l CFA for ankle and knee injections, respectively, appears to be valuable refinement of these models.

neuroscience↗

bioRxiv2024

Decreased BOLD signal variability in middle-aged and older adults on the Autism Spectrum

PurposeAutism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for accelerated or early-onset cognitive and neurological decline in ASD. While it is well established that brain development in children, adolescents and young adults with ASD diverges from neurotypical (NT) peers, it is unknown how brain function is impacted in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings in adults with ASD and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies, likely reflecting declining Gamma-Aminobutyric Acid (GABA) activity, and is associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. MethodsThe study assessed BSV in a cohort of adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested for main effects of diagnostic group (ASD, NT), age and group-by-age interactions (controlling for RMSD). LimitationsOur cross-sectional data and small sample size highlight the need for longitudinal analyses in larger cohorts, alongside exploring links to cognitive function. Additionally, psychotropic medications used by our cohort of adults on the autism spectrum may have affected BSV. ResultsSignificant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT group. ConclusionThese findings suggest that BSV decreases may occur earlier in adults on the autism spectrum compared to their neurotypical peers, possibly indicating accelerated aging. However, given limited prior research, additional longitudinal analyses will be necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function.

neuroscience↗

bioRxiv2019

Tractostorm: Rater reproducibility assessment in tractography dissection of the pyramidal tract

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called \"virtual dissection\". Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. The contribution of this study is to provide the first large-scale, international, multi-center variability assessment of the \"virtual dissection\" of the pyramidal tract (PyT). Eleven (11) experts and thirteen (13) non-experts in neuroanatomy and \"virtual dissection\" were asked to perform 30 PyT segmentation and their results were compared using various voxel-wise and streamline-wise measures. Overall the voxel representation is always more reproducible than streamlines ({approx}70% and {approx}35% overlap respectively) and distances between segmentations are also lower for voxel-wise than streamline-wise measures ([3/4]3mm and [3/4]umm respectively). This needs to be seriously considered before using tract-based measures (e.g. bundle volume versus streamline count) for an analysis. We show and argue that future bundle segmentation protocols need to be designed to be more robust to human subjectivity. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction techniques in this era of open and collaborative science.

neuroscience↗