TY - JOUR

T1 - Differential gene expression in degenerative lumbar discs from the Russian disc degeneration study (RuDDS) biobank

AU - Тяпкин, Александр Вячеславович

AU - Иванов, Артемий Александрович

AU - Леонова, Ольга Николаевна

AU - Krutko, Aleksandr V.

AU - Peleganchuk, Alexey V.

AU - Фишман, Вениамин Семенович

AU - Елгаева, Елизавета Евгеньевна

AU - Цепилов, Яков Александрович

N1 - Conference code: 57

PY - 2024

Y1 - 2024

N2 - Background/Objectives: Degeneration of intervertebral discs (IVDs) can lead to lumbar disc degeneration disease (LDDD), contributing to low back pain, the leading cause of disability worldwide. Despite extensive research, the precise molecular mechanisms underlying LDDD remain unclear. Here, we investigate gene expression differences between conditionally healthy and degenerative IVD from patients in the Russian disc degeneration study (RuDDS) cohort.Methods: Intraoperative IVD fragments, including 14 conditional control samples (Pfirrmann grades I-III, M51.3, M51.8 ICD-10 codes) and 21 case samples (Pfirrmann grades IV-V, M51.1 ICD-10 code), were subjected to strand-specific paired-end RNA-sequencing using DNBSEQ platform. Read alignment and gene-level quantification were performed with STAR tool and summarizeOverlaps function from GenomicAlignments R package, respectively. Using DESeq2 R package, we performed quality control of count data and identified differentially expressed genes (DEGs) with an IHW-adjusted p-value threshold of 0.05. DAVID 2021 was utilized for GO annotation. BisqueRNA was used for cellular decomposition, based on scRNA-seq IVD atlas data. TPM values were calculated with RNA-SeQC, following GTEx V8 guidelines.Results: Five case samples failed quality control. Cellular decomposition of remaining samples confirmed high percentage of chondrocytes (over 70%). We found 87 protein-coding DEGs (74 upregulated, 13 downregulated), including known LDDD-associated genes, such as TREM1, FOXC2. Enriched GO terms included skeletal system development and the Wnt signaling pathway.Conclusion: We identified DEGs enriched in relevant GO terms, suggesting potential drug targets for LDDD treatment.Grants: The study was supported by the Russian Science Foundation (RSF) grant No. 22-15-20037 and the Government of the Novosibirsk region.Conflict of Interest: None declared

AB - Background/Objectives: Degeneration of intervertebral discs (IVDs) can lead to lumbar disc degeneration disease (LDDD), contributing to low back pain, the leading cause of disability worldwide. Despite extensive research, the precise molecular mechanisms underlying LDDD remain unclear. Here, we investigate gene expression differences between conditionally healthy and degenerative IVD from patients in the Russian disc degeneration study (RuDDS) cohort.Methods: Intraoperative IVD fragments, including 14 conditional control samples (Pfirrmann grades I-III, M51.3, M51.8 ICD-10 codes) and 21 case samples (Pfirrmann grades IV-V, M51.1 ICD-10 code), were subjected to strand-specific paired-end RNA-sequencing using DNBSEQ platform. Read alignment and gene-level quantification were performed with STAR tool and summarizeOverlaps function from GenomicAlignments R package, respectively. Using DESeq2 R package, we performed quality control of count data and identified differentially expressed genes (DEGs) with an IHW-adjusted p-value threshold of 0.05. DAVID 2021 was utilized for GO annotation. BisqueRNA was used for cellular decomposition, based on scRNA-seq IVD atlas data. TPM values were calculated with RNA-SeQC, following GTEx V8 guidelines.Results: Five case samples failed quality control. Cellular decomposition of remaining samples confirmed high percentage of chondrocytes (over 70%). We found 87 protein-coding DEGs (74 upregulated, 13 downregulated), including known LDDD-associated genes, such as TREM1, FOXC2. Enriched GO terms included skeletal system development and the Wnt signaling pathway.Conclusion: We identified DEGs enriched in relevant GO terms, suggesting potential drug targets for LDDD treatment.Grants: The study was supported by the Russian Science Foundation (RSF) grant No. 22-15-20037 and the Government of the Novosibirsk region.Conflict of Interest: None declared

UR - https://www.nature.com/articles/s41431-024-01733-5

M3 - Article

VL - 32

SP - 996

EP - 997

JO - European journal of human genetics

JF - European journal of human genetics

SN - 1018-4813

IS - S2

M1 - EP06.052

T2 - 57th European Society of Human Genetics Conference

Y2 - 1 June 2024 through 4 June 2024

ER -