Work

Genetically supported protein signals and ferroptosis-related cell states in human intervertebral disc degeneration: local pQTL–FinnGen screening integrated with nucleus pulposus single-cell RNA sequencing

Year: 2026

Type: article

Abstract: Background: Intervertebral disc degeneration (IVDD) involves nucleus pulposus (NP) cell dysfunction, inflammatory remodeling, and oxidative stress. Genetic support for circulating protein signals and their cell-type-specific context remains incompletely defined. Methods: We integrated deCODE cis-pQTL data with FinnGen R12 M13_INTERVERTEB and human NP scRNA-seq (GSE153066). Local MR screening used harmonized variants with Benjamini-Hochberg correction. The scRNA-seq analysis retained 70,622 cells from 16 libraries and used library-level pseudobulk comparisons. A qPCR validation experiment in PMA-differentiated THP-1 cells (ATCC TIB-202) evaluated MST1, SAA1, BPI, and GCLM under an inflammatory condition. Results: Four multi-SNP signals passed correction: MST1 showed higher endpoint odds (OR = 1.057, q = 4.15 × 10-6), whereas DLK1 (OR = 0.933, q = 0.016), ITIH1 (OR = 0.926, q = 0.016), and SAA1 (OR = 0.927, q = 0.023) showed inverse associations. TP53I3 and BPI remained nominal exploratory signals. TFRC showed a BH-positive single-SNP result (OR = 1.471, q = 0.023). ScRNA-seq resolved eight broad cell populations and demonstrated between-library heterogeneity; nominal macrophage-composition and selected expression differences did not survive within-panel correction. In the qPCR experiment, relative expression was 1.34 for MST1, 0.31 for SAA1, 3.46 for BPI, and 1.70 for GCLM (control = 1.0; n = 4 independent biological replicates/group; all Welch P < 0.001), consistent with the scRNA-seq directions. Conclusions: The study identifies genetically supported protein signals and ferroptosis-related cellular expression patterns while separating genetic screening from transcriptomic localization. The qPCR experiment provides orthogonal experimental support for selected candidate expression changes in the THP-1 inflammatory model.

Source: Frontiers in Cell and Developmental Biology

DOI: 10.3389/fcell.2026.1944218

Authors: Guangying Tang, Xinjun Wu, Yongchun Lin, Zhiyu Tang, He Liang

Institution: Chinese People's Liberation Army

Language: English

Topic: Spine and Intervertebral Disc Pathology

Subfield: Orthopedics and Sports Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801