Biology subjects

Stott, S.

Publications and source records attributed to Stott, S..

3 recordsLinked to original sources

bioRxiv2026

Quantitative imaging of schwannoma captures heterogeneity and accelerates preclinical testing, revealing distinct impacts of targeted therapies

Schwannomas are debilitating hallmarks of familial schwannomatoses and common sporadic tumors that form on spinal and cranial nerves. Drug-based therapies for schwannoma are desperately needed but their development has been extremely slow and disappointing, impeded particularly by the poorly understood and surprisingly complex and heterogeneous biology of schwannomas, and by the inefficient use of physiologically relevant in vivo preclinical models. We have addressed these gaps by developing a quantitative imaging-centered workflow that allows both a deep analysis of schwannoma development and accelerated preclinical testing in a widely used genetically engineered mouse model of neurofibromatosis type 2-related schwannomatosis (NF2-SWN). We deployed our workflow to study schwannoma development and to test two clinically relevant drugs (rapamycin and brigatinib) head-to-head. Our results uncovered the very early onset of heterogeneity and macrophage recruitment to initiating schwannomas, and the unexpectedly distinct impacts of the two drugs on both, highlighting the value of the pipeline for rapid, innovative future drug-testing.

cancer biology↗

bioRxiv2024

Extracellular Vesicles heterogeneity through the lens of multiomics

Extracellular vesicles (EVs) are heterogenous in size, biogenesis, cargo and function. Beside small EVs, aggressive tumor cells release a population of particularly large EVs, namely large oncosomes (LO). This study provides the first resource of label-free quantitative proteomics of LO and small EVs obtained from distinct cancer cell types (prostate, breast, and glioma). This dataset was integrated with a SWATH Proteomic assay on LO, rigorously isolated from the plasma of patients with metastatic prostate cancer (PC). Proteins enriched in LO, which were identified also at the RNA level, and found in plasma LO significantly correlated with PC progression. Single EV RNA-Seq of the PC cell-derived LO confirmed some of the main findings from the bulk RNA-Seq, providing first evidence that single cell technologies can be successfully applied to EVs. This multiomics resource of cancer EVs can be leveraged for developing a multi-analyte approach for liquid biopsy.

cancer biology↗

bioRxiv2020

Single cell transcriptional and functional analysis of human dopamine neurons in 3D fetal ventral midbrain organoid like cultures

Transplantation of midbrain dopamine (DA) neurons for the treatment of Parkinsons disease (PD) is a strategy that has being extensively explored and clinical trials using fetal and stem cell-derived DA neurons are ongoing. An increased understanding of the mechanisms promoting the generation of distinct subtypes of midbrain DA during normal development will be essential for guiding future efforts to precisely generate molecularly defined and subtype specific DA neurons from pluripotent stem cells. In this study, we used droplet-based scRNA-seq to transcriptionally profile a large number of fetal cells from human embryos at different stages of ventral midbrain (VM) development (6, 8, and 11 weeks post conception). This revealed that the emergence of transcriptionally distinct cellular populations was evident already at these early timepoints. To study late events of human DA differentiation and functional maturation, we established a primary fetal 3D culture system that recapitulates key molecular aspects of late human DA neurogenesis and sustains differentiation and functional maturation of DA neurons in a physiologically relevant cellular context. This approach allowed us to define the molecular identities of distinct human DA progenitors and neurons at single cell resolution and construct developmental trajectories of cell types in the developing fetal VM. Overall these findings provide a unique transcriptional profile of developing fetal VM and functionally mature human DA neurons, which can be used to quality control stem cell-derived DA neurons and guide stem cell-based therapies and disease modeling approaches in PD.

neuroscience↗