Biology subjects

Maas, R.

Publications and source records attributed to Maas, R..

5 recordsLinked to original sources

bioRxiv2026

Single-cell multi-omic analyses resolve the cellular diversity of ALK/ROS1/MET/NTRK-fused gliomas in infants and older children

Pediatric cancers are thought to arise from dysregulation of developmental programs, otherwise tightly regulated in time and space. Infant-type hemispheric gliomas (IHGs) arise in early childhood, driven by characteristic ALK/ROS1/MET/NTRK receptor tyrosine kinase (RTK) gene fusions. We dissected the cellular hierarchies of 24 fusion-positive gliomas, spanning infants through adolescents, using single-cell and single-nucleus RNA/ATAC-seq, and spatial transcriptomics. We identified five cancer cell states, with radial glia-like cells at the apex of a neoplastic hierarchy resembling neuronal- and glial-like trajectories. Neuronal-like cells were enriched in most IHGs but diminished in ROS1-fused IHGs and older patients. Integration of chromatin profiling revealed FOS/JUN-driven oncogenic programs and high inferred plasticity across all cancer cell populations. Myeloid cells, the most abundant non-neoplastic population, comprised distinct subgroups, suggesting context-dependent functions. Despite lacking high-order structure, spatial transcriptomics revealed discrete cellular niches within IHGs. Collectively, our findings elucidate the cellular states and developmental programs underlying IHGs and RTK-fused gliomas in older patients, opening new avenues for research and therapy innovation.

cancer biology↗

bioRxiv2024

The Neural Blueprint of Stress Susceptibility: Brain-wide neuronal activity associated with the consequences of stress

Understanding the neurobiological mechanisms of stress susceptibility is key to advancing our insight into stress-related psychopathology like post-traumatic stress disorder (PTSD). Preclinical animal models however typically lack translationally relevant brain readouts. Here, we used a mouse model for severe stress, segregating mice into stress-susceptible and resilient groups. We analyzed and contrasted their whole-brain neuronal activity pre-, peri- and post-stress exposure and compared functional connectivity of the salience (SN), default mode (DMN) and executive control network (lateral cortical network (LCN) in rodents). We found that stress-susceptible mice exhibited pre-existing hyperactivity in the lateral orbital area, a potential risk factor for stress vulnerability, and heightened retrosplenial cortex activity peri- and post-stress, potentially contributing to maladaptive fear memory. Upon stress exposure, susceptible mice showed strong recruitment of visual and memory-related areas, whereas resilient mice displayed marked reductions in retrosplenial activity and increased activation in the agranular insula and ventral striatum. Observations of enhanced intra-SN and SN-DMN connectivity in susceptible mice mirrored those observed in individuals with PTSD. Moreover, susceptible mice displayed aberrant DMN-LCN network pre- and peri-stress. These findings highlight the importance of dynamic network interactions in stress susceptibility and suggest novel brain region targets for (early) intervention.

neuroscience↗

bioRxiv2024

Glycoinformatic profiling of label-free intact heparan sulfate oligosaccharides

Heparan sulfates (HS) are a group of heterogenous linear, sulfated polysaccharides that play a role in in health and many diseases including cancer, cardiovascular, and kidney diseases. The structural variety of HS has greatly challenged the development and utility of HS analytics, particularly for native structures, leaving a significant gap in HS technologies for clinical application. Mass spectrometry (MS)-based profiling with bioinformatics offers a top-down approach that can retain variety in large data sets. Using healthy human plasmas, we developed an MS glycoprofiling approach for native HS oligosaccharides, which retains the structural complexity of each individual HS chain and generates an HS index (or Heparan-ome) for each patient. As a proof of concept, analysis of 56 plasma samples ranging from 6 groups of kidney disease patients revealed a new subset cluster (20%, 4/20) of membranous glomerulopathy (MG) patients with distinct HS profiles, highlighting the potential of HS glycoprofiling as a powerful new approach into clinical practice, which warrants future development into clinical diagnostics of kidney and other diseases. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/613784v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@6dac34org.highwire.dtl.DTLVardef@449da1org.highwire.dtl.DTLVardef@c8eb88org.highwire.dtl.DTLVardef@df4deb_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2021

How much pollen do solitary bee larvae consume? Or establishing realistic exposure estimates of solitary bee larvae via pollen for the use in risk assessment

Bees foraging in agricultural habitats can be exposed to plant protection products. In order to limit the risk of adverse events to occur a robust risk assessment is needed, which requires reliable estimates for the expected exposure. Especially the exposure pathways to developing solitary bees are not well described and in the currently proposed form rely on limited information. To address this topic, we used a published data set on the volume of pollen solitary bees provide for their larvae to build two scaling models predicting the amount of protein and pollen developing solitary bees need based on adult body weight. We test our models using both literature and experimental data, which both support the validity of the presented models. Using scaling models in the bee risk assessment could complement existing risk assessment approaches, facilitate the further development of accurate risk characterization for solitary bees and ultimately will help to protect them during their foraging activity in agricultural settings.

ecology↗

bioRxiv2020

ALX1-related Frontonasal Dysplasia Results From Defective Neural Crest Cell Development and Migration

A pedigree of subjects with frontonasal dysplasia (FND) presented with bilateral oblique facial clefts and ocular phenotypes. Genome sequencing and analysis identified a L165F missense variant in the homeodomain of the transcription factor ALX1 which was imputed to be pathogenic. Induced pluripotent stem cells (iPSC) were derived from the subjects and differentiated to neural crest cells (NCC). NCC derived from ALX1L165F/L165F iPSC were more sensitive to apoptosis, showed an elevated expression of several neural crest progenitor state markers, and exhibited impaired migration compared to wild type controls. NCC migration was also evaluated in vivo using lineage tracing in a zebrafish model, which revealed defective migration of the anterior NCC stream that contributes to the median portion of the anterior neurocranium, phenocopying the clinical presentation. Analysis of human NCC culture media revealed a change in the level of bone morphogenic proteins (BMP), with a low-level of BMP2 and a high level of BMP9. Soluble BMP2 and BMP9 antagonist treatments were able to rescue the defective migration phenotype. Taken together, these results demonstrate a mechanistic requirement of ALX1 in NCC development and migration.

cell biology↗