The transcriptome of CD14

Summary

Single-cell profiling identified a CD14+ monocyte-derived 230-gene score that consistently predicted outcomes in IPF and was validated across PBMC, BAL, and lung tissue cohorts (overall n=1054). The study traced cellular origin, explored function, and used connectivity mapping and LASSO to propose drug candidates and a parsimonious gene subset.

Key Findings

• A CD14+ monocyte 230-gene up-score predicted IPF outcomes across PBMC, BAL, and lung tissue cohorts (overall n=1054).
• Validation included flow cytometry, independent scRNA-seq datasets, and deconvolution analyses to confirm cellular origin and function.
• Connectivity Map and LASSO identified potential drug candidates and a reduced gene set with prognostic utility.

Clinical Implications

Supports development of blood-based prognostic assays and stratified clinical trials in IPF; may inform selection of patients for aggressive therapy or transplant evaluation.

Limitations

• Observational design; causal mechanisms not directly tested
• Abstract truncation limits access to full quantitative performance metrics in this summary

Future Directions

Prospective clinical validation of a blood-based assay, integration into prognostic models, and interventional trials using the signature for risk stratification.