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Updated: Jan 13, 2026
Single-cell Profiling of Developing and Mature Retinal Neurons
Published on: April 19, 2012
Integrative analysis of single-cell and bulk RNA sequencing data for discovery of senescent TAMs prognostic
Sitong Qiu1, Youyang Hu1, Yiming Wang1
1Department of Pediatric Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
Background:
Tumor-associated macrophages (TAMs) comprise heterogeneous subtypes with context-dependent functions in tumor immunity. Although macrophage senescence influences diverse diseases, its role in neuroblastoma (NB) progression remains undefined.
Methods:
Single-cell RNA sequencing (scRNA-seq) data from NB samples (GEO: GSE147766) were analyzed to identify TAM subtypes. Senescence-associated signatures were characterized via pseudotime trajectory, cell-cell communication, and functional assays. A prognostic model was developed using Cox/LASSO regression and validated in independent cohorts (TARGET-NBL, E-MTAB-8248). Drug sensitivity and immune microenvironment differences were compared between risk groups. In vitro validation assessed EIF5's role in TAM senescence and NB progression.
Results:
We identified a senescent TAM subset (C0) exhibits a hybrid M1/M2 state with a dominance of M2-like features. Pseudotime analysis revealed differentiation from non-senescent TAMs (C1), accompanied by upregulated LILRB1, LILRB2, IL10, and CXCL8. A 7-gene prognostic signature (AMD1, ARL4A, BRD2, DDX3X, EIF5, SLC43A2, ZEB2) stratified patients into risk groups with distinct survival (P < 0.001). High-risk patients displayed impaired anti-tumor immunity (reduced CD8⁺ T cells, elevated TIDE scores) and differential drug sensitivity. EIF5 knockdown suppressed senescence markers (p21/p16) in macrophages and inhibited NB cell proliferation/migration.
Conclusions:
Senescent TAMs influence NB immunosuppression and progression. EIF5 is a key regulator of TAM senescence and a potential therapeutic target. Our risk model may guide clinical stratification and targeted interventions.
