Biology subjects

Rice, S. J.

Publications and source records attributed to Rice, S. J..

3 recordsLinked to original sources

bioRxiv2026

Single-cell proteomics resolves major cell populations and protein-defined chondrocyte states in the adult human osteoarthritic joint

Objective Single-cell RNA sequencing has transformed our understanding of cellular heterogeneity within osteoarthritic (OA) joint tissues, yet transcript abundance provides only an indirect measure of cellular phenotype and function. Recent advances in mass spectrometry now enable proteins to be measured directly at single-cell resolution. Here, we applied single-cell proteomics (SCP) to primary human OA cartilage and synovium to determine whether cellular heterogeneity within the diseased joint can be resolved directly at the proteome level. Design Cartilage and synovium were obtained from patients undergoing total knee arthroplasty for OA. Low-input proteomic profiling was first performed to establish proteome depth from limited cell numbers and validate biologically relevant clustering. SCP was then applied to individual cells, followed by unsupervised clustering, differential protein abundance analysis and iterative biological annotation. Results Low-input proteomics identified 7,800 proteins from 1,000 cells while retaining tissue- and cell-associated biological differences. Across the SCP dataset, ~2,300 unique proteins were detected, resolving chondrocyte, synovial fibroblast and immune-cell populations that closely paralleled those previously defined by single-cell transcriptomics. Higher-resolution analysis distinguished lining and sublining fibroblasts, discrete immune populations and multiple protein-defined chondrocyte states. Conclusions SCP enables direct characterisation of cellular heterogeneity within the human OA joint at the level of the proteome. By independently recovering established cellular populations while revealing protein-defined chondrocyte states, our findings establish SCP as a powerful complement to single-cell transcriptomics and open a new route to investigating functional cellular states and disease mechanisms that cannot be inferred from RNA abundance alone.

genetics↗

bioRxiv2023

Surface modification of multilayer graphene neural electrodes by local printing of platinum nanoparticles using spark ablation

In this paper, we present the surface modification of multilayer graphene neural electrodes with platinum (Pt) nanoparticles (NPs) using spark ablation. This method yields an individually selective local printing of NPs on an electrode surface at room temperature in a dry process. NP printing is performed as a post-process step to enhance the electrochemical characteristics of graphene electrodes. The NP-printed electrode shows significant improvements in impedance, charge storage capacity (CSC), and charge injection capacity (CIC), versus the equivalent electrodes without NPs. Specifically, electrodes with 40% NP surface density demonstrate 4.5 times lower impedance, 15 times higher CSC, and 4 times better CIC. Electrochemical stability, assessed via continuous cyclic voltammetry (CV) and voltage transient (VT) tests, indicated minimal deviations from the initial performance, while mechanical stability, assessed via ultrasonic vibration, is also improved after the NP printing. Importantly, NP surface densities up to 40% maintain the electrode optical transparency required for compatibility with optical imaging and optogenetics. These results demonstrate selective NP deposition and local modification of electrochemical properties in neural electrodes for the first time, enabling the cohabitation of graphene electrodes with different electrochemical and optical characteristics on the same substrate.

neuroscience↗

bioRxiv2020

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

ObjectiveOsteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC, and methylation quantitative trait loci (mQTLs) at PLEC CpGs in cartilage. This implies that methylation links chondrocyte genotype and phenotype, thus driving the functional effect. PLEC encodes plectin, a cytoskeletal protein that enables tissues to respond to mechanical forces. We sought to assess whether PLEC functional effects were cartilage specific. MethodCartilage, fat pad, synovium and peripheral blood were collected from patients undergoing arthroplasty. PLEC CpGs were analysed for mQTLs and allelic expression imbalance (AEI) was performed. We focussed on previously reported mQTL clusters neighbouring cg19405177 and cg14598846. Plectin was knocked down in a mesenchymal stem cell (MSC) line using CRISPR/Cas9 and cells phenotyped by RNA-sequencing. ResultsNovel mQTLs were discovered in fat pad, synovium and peripheral blood at both clusters. The genotype-methylation effect of rs11780978 was stronger in cg14598846 than in cg19405177 and stronger in joint tissues than in peripheral blood. We observed AEI in synovium in the same direction as for cartilage. Knocking-down plectin impacted on pathways reported to have a role in OA, including Wnt signalling, glycosaminoglycan biosynthesis and immune regulation. ConclusionsSynovium is also a target of the rs11780978 OA association functionally operating on PLEC. In fat pad, mQTLs were identified but these did not correlate with PLEC expression, suggesting the functional effect is not joint-wide. Our study highlights interplay between genetic risk, DNA methylation and gene expression in OA, and reveals clear differences between tissues from the same diseased joint.

genetics↗