Biology subjects

Taylan, F.

Publications and source records attributed to Taylan, F..

3 recordsLinked to original sources

bioRxiv2026

Spatial mapping of pediatric brain tumors across diagnoses and relapses

We present a spatial transcriptomic atlas of 19 pediatric brain tumor patients spanning nine major and rare diagnoses, including seven relapses, revealing their spatial cellular and molecular organization. Each tumor section resolves into 2 - 4 recurrent spatial archetypes across 11 biological themes, with some mirroring developmental lineage patterns - for example, oligodendrocyte-lineage programs in pilocytic astrocytomas. Spatially inferred copy-number analysis identifies relapse-associated putative clones. In one rare embryonal tumor, spatial niches in the primary tumor harboring putative clones colocalized with an archetype enriched for nervous system development and glioblast-lineage programs. In one ependymoma and one pilocytic astrocytoma, relapse-associated putative clones preferentially localized to the vasculature, suggesting regrowth during relapse may be seeded by clonal selection of residual tumor cells within specialized microenvironmental niches. This resource provides an open-access spatially resolved map via an interactive viewer to inform research on pediatric brain tumor ecosystems, relapse biology, and therapeutic strategies.

cancer biology↗

bioRxiv2025

Cumulative microscopy reveals cellular states in fibroblasts from patients with genetic disorders

Analysis of cellular states and signaling trajectories can provide insights into causes of disease. We developed cumulative microscopy, a method to perform cyclical imaging without elution or quenching steps. Cumulative microscopy computationally extracts individual signals from accumulating fluorescence during sequential imaging. We used cumulative microscopy to quantitatively assess cell cycle and stress markers in individual primary fibroblasts from patients with rare genetic proliferative disorders with increased cancer risk. Neural network-based analysis of cumulative microscopy data suggested that cells from patients with Cartilage-hair hypoplasia (CHH), but not Mulibrey Nanism (MUL), showed replication stress. We analyzed cell states and cell trajectories and found that a subset of cells from patients with CHH showed spontaneous replication stress, followed by cell cycle exit in both G1 and G2 phase. We note that replication stress potentially could underlie both proliferative defects and increased cancer risk in CHH patients and conclude that cumulative microscopy is an efficient, quantitative, and generalizable approach to multiplex microscopy. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/668398v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@4bcd0dorg.highwire.dtl.DTLVardef@83262corg.highwire.dtl.DTLVardef@3f3f13org.highwire.dtl.DTLVardef@46174b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Rare coding variants in NOX4 link high superoxide levels to psoriatic arthritis mutilans

Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis. PAM is characterized by erosions of the small joints of hands and feet and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no candidate susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM. We performed massive parallel sequencing of sixty-one patients genomes from the PAM Nordic cohort. We validated the rare variants found by Sanger sequencing and genotyped additional psoriasis, psoriatic arthritis, and control cohorts. We then tested the role of the variants using in vivo and in vitro models. We found rare variants with a minor allele frequency (MAF) below 0.0001 in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). ROS are highly reactive molecules important role in the regulation of signal transduction. NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that the NOX4 variants found in this study increase the levels of ROS both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, opening the possibility for a potential therapeutic target.

genetics↗