Transcriptomic and proteomic analysis of osteogenesis imperfecta disease-specific induced pluripotent stem cells

Osteogenesis imperfecta (OI) is a rare genetic bone disorder for which treatment options remain limited. Disease-specific induced pluripotent stem cells (iPSCs) offer a valuable model to investigate its underlying pathological mechanisms.

Peripheral blood cells from two OI patients were reprogrammed into iPSCs. Transcriptomic sequencing and proteomic analysis were employed to systematically identify differentially expressed genes (DEGs) and proteins (DEPs) between OI-iPSCs and normal iPSCs. Bioinformatics approaches were subsequently applied for enrichment analysis and protein-protein interaction network investigation.

OI-iPSCs were successfully established. Integrated multi-omics analysis identified 671 common DEGs and 636 common DEPs. These molecules were significantly enriched in metabolic pathways, with the oxidative phosphorylation pathway being particularly prominent. Further cross-omics screening revealed 22 genes that were differentially expressed at both the mRNA and protein levels. Among these, the focal adhesion protein VCL emerged as a central hub within the protein-protein interaction network.

Through multi-omics analysis, this study revealed widespread dysregulation of metabolic pathways in OI-iPSCs, suggesting that targeted interventions on specific metabolic pathways may represent a novel therapeutic strategy for OI. VCL emerged as a key candidate molecule, warranting further functional validation in subsequent studies. These findings provide new insights into the mechanisms of OI and potential avenues for therapeutic development.