Biology subjects

Mitsios, N.

Publications and source records attributed to Mitsios, N..

3 recordsLinked to original sources

bioRxiv2026

The genetic architecture of dementia risk: how Alzheimer's disease vulnerability converges on lipid metabolism and immune cell networks

Although genome-wide association studies (GWAS) have identified numerous dementia risk loci, their cell-type and tissue-specific contexts remain largely unresolved. We introduced HPA GeneSet Explorer, a statistical pipeline designed to systemically map Genome wide association study (GWAS) disease risk genes across the Human Protein Atlas (HPA). This approach generates a multiscale transcriptomic map of genetic risk, spanning systemic organs, brain regions, and cell types. Applying this framework to Alzheimers disease (AD), Lewy body dementia (DLB), and Frontotemporal dementia (FTD) revealed convergent neuronal enrichment in all three diseases. In addition, we identified AD-specific enrichment in immune system and liver associated gene modules, along with DLB-specific enrichment in ciliary modules. By mapping these vulnerabilities in non-demented samples, we provide a blueprint of the baseline vulnerability hotspots that can precede clinical neurodegeneration, offering new targets for disease-specific therapies and biomarker discovery.

neuroscience↗

bioRxiv2024

Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution

Intracerebral hemorrhage (ICH) is a severe and widespread disease that results in high mortality and morbidity. Despite significant advances made in clinical and preclinical research, the prognosis of ICH remains poor due to an incomplete understanding of the complex pathological responses. To address this challenge, we generated single-cell resolution spatiotemporal transcriptomic maps of mouse brain 1, 3, 7, 14, and 28 days after ICH. Our analysis revealed the cellular constituents and their dynamic responses following ICH. We found changes in gene expression that are indicative of active phagocytosis and lipid processing in the lesion core and identified genes associated with brain repair at the lesion border. Persistent lipid accumulation culminated in the phenotypic transition of macrophages into foam cells. Furthermore, our results demonstrate that ICH could stimulate neural stem cells in the subventricular zone, thereby enhancing neurogenesis in this niche. This study provides a spatiotemporal molecular atlas of mouse ICH that advances the understanding of both local and global responses of brain cells to ICH and offers a valuable resource that can aid the development of novel therapies for this devastating condition.

neuroscience↗

bioRxiv2021

Regulatory FOXP3+ T cells in uterine sarcomas are associated with favorable prognosis, low extracellular matrix expression and reduced YAP activation

PurposeUterine sarcomas are rare but deadly malignancies without effective treatment. The goal of this study was to characterize and identify potential mechanisms underlying observed variations in the immune microenvironment of different sarcoma subtypes, using integrated clinicopathological and molecular methods. Experimental designFifty-eight cases of uterine sarcoma with full clinicopathological annotation were analyzed for their immune landscape in the tumor microenvironment, gene, and protein expression. Cases included leiomyosarcoma (LMS; n=13), low-grade endometrial stromal sarcoma (ESS; n=16), undifferentiated uterine sarcoma (UUS; n=26), and YWHAE-FAM22 translocation-bearing ESS (YFAM; n=3). Image analysis was used to quantify immune cells and immune regulatory proteins. Gene ontology and network enrichment analysis of matching transcriptomic data was used to relate over- and under expressed genes to pathways and further to the immune phenotype and clinicopathological findings. ResultsImmune cell characterization revealed overall prevalence of regulatory T cells and the pro-tumor M2-like macrophages. Cytotoxic T cells were only found in ESS and UUS tumors. Expression of immune regulatory proteins was heterogeneous, with PD-L1 being undetectable. Hierarchical clustering of patients showed four immune signatures independent of tumor type, where infiltration of non-exhausted FOXP3+ cells and M1-like macrophages were associated with greater overall survival. High CD8+/FOXP3+ ratio in UUS and ESS was associated with poor survival and upregulation of extracellular matrix (ECM)-related genes and proteins and YAP nuclear localization. ConclusionsUterine sarcomas present distinct immune signatures with prognostic value, independent of tumor type. This study suggests that the ECM is a potential regulator of the immune microenvironment in uterine sarcomas.

cancer biology↗