Biology subjects

Sanderson, B.

Publications and source records attributed to Sanderson, B..

5 recordsLinked to original sources

bioRxiv2026

Dietary Oxysterols Reprogram Hepatic Lipid Metabolism and Reshape the Gut Metabolome-Microbiome Interface

Dietary oxysterols are biologically active cholesterol oxidation products ubiquitous in Western diets, yet their systemic effects on host metabolism and the gut microbiome remain largely unexplored. Here, we employed an integrated multi-omics approach - shotgun metagenomics, quantitative proteomics, untargeted metabolomics, and bulk RNA-seq - to characterize the impact of DOxS exposure on the gut-liver axis in rats fed a Western diet (WD vs. WD-DOxS). Hepatic proteomics revealed near-complete suppression of the mevalonate/cholesterol biosynthesis pathway, particularly in males, while de novo lipogenesis enzymes (Scd1, Fasn, Plin2) were paradoxically upregulated, consistent with dual oxysterol signaling through SREBP inhibition and LXR activation. Bile acid synthesis was concurrently suppressed, confirmed by metabolomics. Strikingly, RNA-seq across liver, heart, and brain detected virtually no differentially expressed genes, establishing that DOxS act predominantly through post-transcriptional mechanisms. In the gut, DOxS increased microbial -diversity while depleting Limosilactobacillus reuteri, with concomitant loss of the barrier-protective metabolite 3-indoleacrylic acid. Tissue-specific responses were widespread, with liver and colon frequently mounting opposing metabolic and immune responses to the same dietary challenge. Cross-omics integration revealed convergent microbiome-metabolite axes connecting microbial remodeling to both hepatic lipid reprogramming and colonic barrier disruption. These findings reposition dietary oxysterols from food-quality markers to active modulators of the gut-liver axis, with implications for metabolic disease and intestinal barrier integrity.

biochemistry↗

bioRxiv2025

Single-cell transcriptomic profiling of C. elegans Q neuroblast lineage during migration and differentiation

Proper migration and differentiation of neuroblasts into neurons are essential for the development of a healthy nervous system. In this context, the asymmetrical migration of Caenorhabditis elegans Q neuroblasts provides a powerful model for studying the genetic aspects of neuronal migration in vivo at single-cell resolution. We isolated Q lineage cells at various stages of development using FACS and employed single-cell RNA sequencing to investigate the molecular mechanisms underlying the migration and differentiation of these neuroblasts. We created a robust transcriptomic differentiation map of the Q neuroblast lineage and used established markers to identify each cell in the lineage. Our results revealed novel genes not previously described on these cells and linked the expression of known genes to specific stages of Q lineage progression. Furthermore, functional enrichment and imaging provided evidence that the parent Q cells are initially specified with an epithelial-like identity and undergo epithelial-mesenchymal transition during the early stages of migration. We also identified novel Wnt-related mechanisms, including left-right asymmetric expression of cwn-1 and cwn-2, and the involvement of the Wnt/{beta}-catenin asymmetry pathway in the Q lineage. Our work offers a high-resolution view of neuroblast development, showcasing the power of single-cell transcriptomics to reveal stage-specific regulatory programs. Author SummaryCell migration and differentiation are critical steps for nervous system formation. Mapping changes in single-cell behavior during this process can greatly improve our understanding of neuronal development. However, the complexity of the human brain presents significant challenges to analyzing these processes in individual cells. Here, we used the Q neuroblast lineage from the nematode worm Caenorhabditis elegans as a model system to investigate the molecular dynamics of neurodevelopment using single-cell RNA sequencing. By analyzing over 6,000 individual cells from the Q lineage, we generated a detailed map showing how each cell in this lineage changes over time. This approach allowed us to identify new genes that had not previously been associated with this system and to identify the expression patterns of known genes at different stages of lineage development. By looking at gene functions at different stages, we also discovered that the parent cells in the lineage initially exhibit an epithelial-like identity before transitioning to neuroblasts and later becoming neurons. Overall, our study gives a clear picture of how gene expression changes as this neuroblast lineage develops, enhancing our understanding of how different genetic programs can influence neural development.

developmental biology↗

bioRxiv2024

Spatiotemporal profiling defines persistence and resistance dynamics during targeted treatment of melanoma

Resistance of BRAF-mutant melanomas to targeted therapy arises from the ability of cells to enter a persister state, evade treatment with relative dormancy, and repopulate the tumor when reactivated. Using spatial transcriptomics in patient derived xenograft models, we capture clonal lineage evolution during treatment, finding the persister state to show increased oxidative phosphorylation, decreased proliferation, and increased invasive capacity, with central-to-peripheral gradients. Phylogenetic tracing identifies intrinsic- and acquired-resistance mechanisms (e.g. dual specific phosphatases, Reticulon-4, CDK2) and suggests specific temporal windows of potential therapeutic efficacy. Using deep learning to analyze histopathological slides, we find morphological features of specific cell states, demonstrating that juxtaposition of transcriptomics and histology data enables identification of phenotypically-distinct populations using imaging data alone. In summary, we define state change and lineage selection during melanoma treatment with spatiotemporal resolution, elucidating how choice and timing of therapeutic agents will impact the ability to eradicate resistant clones. Statement of SignificanceTumor evolution is accelerated by application of anti-cancer therapy, resulting in clonal expansions leading to dormancy and subsequently resistance, but the dynamics of this process are incompletely understood. Tracking clonal progression during treatment, we identify conserved, global transcriptional changes and local clone-clone and spatial patterns underlying the emergence of resistance.

cancer biology↗

bioRxiv2023

Reproductive sexual dimorphisms in two willow species, Salix exigua Nutt. and S. nigra Marshall.

Premise of the ResearchThe prevalence of sexual dimorphisms, which evolve due to contrasting strategies to maximize reproductive success in males and females, is variable among dioecious plant species. In the Salicaceae, many traits have been assessed across many studies, but direct or indirect associations between these traits and reproductive allocation are often neglected. Given the dynamic evolution of sex determination systems and the strong interest in wood production in the family, we wondered whether sexual dimorphisms related to reproduction may have gone unreported. Here, we assess sexual dimorphism in reproductive traits in two species of Salix. Recognition of reproductive sexually dimorphic traits will contribute to understanding the evolution of sex determination systems in the Salicaceae. MethodologyWe conducted observational studies in natural populations to assess the presence of sexual dimorphisms in early spring bud density, catkin number, and flower number per catkin across four sampling periods in Salix exigua. We also analyzed flower number and catkin number per flower in Salix nigra. Pivotal ResultsWe observed no sexual dimorphism in pre-season buds per branch in S. exigua but did find that males produced more flowers per catkin and more catkins per branch than females in both S. exigua and S. nigra. ConclusionsHigher flower numbers in males compared to females is consistent with expectations from intra-sexual selection among males. The presence of reproductive sexual dimorphisms in Salix suggests that sexual selection may affect the evolution of mating strategies in Salix species, and the evolution of the sex determination system within this genus.

plant biology↗

bioRxiv2021

Novel algorithms deriving clinical performance measures from smartphone sensor data collected under a walking test

The modern ubiquity of smartphones which incorporate sensors such as inertial measurement units (IMU) and global positioning system (GPS) receivers, raises the possibility that they might be used as inexpensive devices for clinical performance testing. Here, we report on the development and testing of an app and associated statistical signal processing algorithms, to measure the basic gait properties of step rate, walking speed and distance under an outside short walk test experimental protocol, from digital accelerometry and GPS. We provide extensive details on the assumptions underlying the development of the algorithms. A small set of experiments across a range of conditions and individuals, demonstrate the reliability of the combined app, protocol and algorithms. With reasonable adherence to the test protocol, these experiments show 2% error across all metrics. The emphasis in this paper is on illustrating the design principles which all such systems, aiming to re-purpose consumer smartphones as clinical gait measurement devices, must address.

bioengineering↗