Single-cell multi-omics defines H3K27me3 remodelling in intervertebral disc degeneration with implications for regenerative intervention (SORT-Seq)

Here, we integrated transcriptomic data with repressive histone H3 lysine 27 trimethylation (H3K27me3) profiles at the single-cell level to assess changes in chromatin states and gene expression across this IVD degeneration-associated cell phenotypic transition. H3K27me3 enrichment of key genes involved in IVD development and homeostasis, such as brachyury (TBXT), aligns with the observed attenuation during ageing and degeneration seen in both dog and human IVDs.

This study further demonstrates that eliminating repressive histone marks, together with CRISPR-mediated gene transactivation, enhances TBXT gene expression in human NPCs derived from degenerated aged discs. Our findings underscore how extensive insights gained through single-cell omics can lead to the identification of crucial cellular cues that may enable degenerate NPCs to regain a healthier phenotype.