Catalyst Awardee

Project Description

Deciphering Disease Pathogenesis and Druggable Targets for Degenerative Tendinopathy using an Unbiased, Genome-wide, Single-Cell, Spatial Transcriptomic Approach

Patrick Shu Hang YUNG, FRCSEd | Department of Orthopaedics and Trumatology, The Chinese University of Hong Kong; Pauline Po Yee LUI, PhD
Competition Sponsor:
Research Grants Council of the Hong Kong Special Administrative Region, China
Awardee year: 2022

Degenerative tendinopathy is a chronic musculoskeletal disorder presented with local tendon pain, physical disability and ultimately tendon rupture due to tendon overuse and aging. It is an unmet clinical challenge due to its unclear etio-pathogenesis. Single-cell RNA-sequencing (scRNA-seq) allows the discovery of previously unknown rare cell types/subtypes in normal and diseased tendons in tendinopathy. By adding spatial information to scRNA-seq data, spatial transcriptomics allows cell groups sharing similar and differential gene expression and in-situ cell-to-cell interactions to be identified in the tissue context, transforming our understanding of tissue functional organization. Formalin-fixed and paraffin-embedded (FFPE) tendinopathy and healthy tendon samples represent a rich resource for molecular profiling but is unfortunately incompatible with scRNA-seq due to RNA degradation in extraction. Recent advances in spatial transcriptomics supports the use of FFPE samples for transcriptome sequencing at the cellular level. However, there has been no similar study on FFPE samples of tendinopathy.This study aims to use a ground-breaking spatial transcriptomics approach of FFPE samples for the discovery of key players, biological processes, novel biomarkers, and cell-to-cell interactions, at the single cell and spatial levels, in degenerative tendinopathy. Single-cell spatial transcriptomic data of diseased and healthy FFPE tendon samples will be obtained and analyzed. The expression and co-localization of key genes or cell types in spatial transcriptomics will be verified by fluorescent in-situ hybridization and immunofluorescent staining of consecutive tissue sections and an independent cohort. The study will open new opportunities of using FFPE samples for spatial transcriptomic research in tendon to improve population health.

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