Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
Degeneration of intervertebral discs (IVD), the major connective joint tissues in the vertebral column, is associated with low back pain incidence and severity. Understanding the mechanism of IVD degeneration is key to the control and management of this worldwide disease burden. Sustained proinflammatory stimuli can inhibit normal tissue repair and trigger pathological consequences. IVD degeneration has been linked to an upregulated activity of proinflammatory cytokines. However, the knowledge of these proinflammatory cytokine effects is built on the bulk cell phenotype and the evaluation of selected genes. Its precise impact on cell state and fate of the disc cells remains elusive. Our recent in vivo cell lineage tracing study has indicated that local disc cells may acquire a fibroblast-like state after injury, supporting IVD degeneration involves a process featuring cell dedifferentiation. This project aims to take advantage of the single-cell RNA sequencing to obtain genome-wide transcriptome data from individual cells and delineate the impact of proinflammatory cytokines on disc cell subpopulations. This outcome will facilitate construction of a cell fate profile and lineage hierarchy under the effect of proinflammatory cytokines. The investigation will lead to a more sophisticated way to evaluate the impact of biological stimuli or environmental factors on disc cells, facilitating the development of effective vertebral joint regeneration approaches in future.
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