Characterization of Ferroptosis-Related Genes in Aplastic Anaemia: An Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data.

Introduction: Ferroptosis offers novel perspectives for treating multiple blood-related diseases, yet its role in aplastic anaemia (AA) is rare. This study aimed to explore key ferroptosis-related genes (FRGs) in AA using bulk and single-cell RNA sequencing (scRNA-seq) data.

Methods: scRNA-seq and bulk RNA-seq data, along with FRG lists, were obtained from public databases. Differentially expressed FRGs (DEFRGs) between AA and control samples were identified, followed by functional enrichment and protein-protein interaction analyses. Single-cell analyses were conducted to reveal main cell types in samples and DEFRGs activity in each cell was assessed. Moreover, DEGs between AA and control samples at the cellular level were explored, followed by integration with DEFRGs to determine common key genes. KEGG pathway analysis of these genes was performed at the cellular level. Immune infiltration analysis was used to evaluate the relationship between key genes and immune cells.

Results: A total of 38 DEFRGs were identified, enriched in pathways such as the intrinsic apoptotic signalling pathway. scRNA-seq analysis identified seven cell types, with elevated DEFRGs activity in platelets and stromal cells. Key genes DDIT4 and NCF2, identified through integrated analysis, were involved in autophagy, mTOR signalling, and osteoclast differentiation pathways. Moreover, their expressions were positively correlated with activated dendritic cells in AA samples.

Conclusion: Our findings highlight the roles of DDIT4 and NCF2, in AA progression, providing potential insights for further mechanistic exploration of AA.