A novel multi-omics approach for identifying key genes in intervertebral disc degeneration

Many different cell types and complex molecular pathways are involved in intervertebral disc degeneration (IDD). We used a multi-omics approach combining single-cell RNA sequencing (scRNA-seq), differential gene expression analysis, and Mendelian randomization (MR) to clarify the underlying genetic...

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Main Authors: Xuan Zhao, Qijun Wang, Shuaikang Wang, Wei Wang, Xiaolong Chen, Shibao Lu
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:SLAS Technology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2472630324001055
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author Xuan Zhao
Qijun Wang
Shuaikang Wang
Wei Wang
Xiaolong Chen
Shibao Lu
author_facet Xuan Zhao
Qijun Wang
Shuaikang Wang
Wei Wang
Xiaolong Chen
Shibao Lu
author_sort Xuan Zhao
collection DOAJ
description Many different cell types and complex molecular pathways are involved in intervertebral disc degeneration (IDD). We used a multi-omics approach combining single-cell RNA sequencing (scRNA-seq), differential gene expression analysis, and Mendelian randomization (MR) to clarify the underlying genetic architecture of IDD. We identified 1,164 differentially expressed genes (DEGs) across four important cell types associated with IDD using publicly available single-cell datasets. A thorough gene network analysis identified 122 genes that may be connected to programmed cell death (PCD), a crucial route in the etiology of IDD. SLC40A1, PTGS2, and GABARAPL1 have been identified as noteworthy regulatory genes that may impede the advancement of IDD. Furthermore, distinct cellular subpopulations and dynamic gene expression patterns were revealed by functional enrichment analysis and pseudo-temporal ordering of chondrocytes. Our results highlight the therapeutic potential of GABARAPL1, PTGS2, and SLC40A1 targeting in the treatment of IDD.
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publishDate 2024-12-01
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series SLAS Technology
spelling doaj-art-c0ff7f6bbe6b43f8898a7b7ad7337ef32025-08-20T02:36:58ZengElsevierSLAS Technology2472-63032024-12-0129610022310.1016/j.slast.2024.100223A novel multi-omics approach for identifying key genes in intervertebral disc degenerationXuan Zhao0Qijun Wang1Shuaikang Wang2Wei Wang3Xiaolong Chen4Shibao Lu5Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, ChinaDepartment of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, ChinaDepartment of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, ChinaDepartment of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, China; Corresponding authors at: Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China.Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, China; Corresponding authors at: Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China.Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Geriatric Diseases, Beijing, China; Corresponding authors at: Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China.Many different cell types and complex molecular pathways are involved in intervertebral disc degeneration (IDD). We used a multi-omics approach combining single-cell RNA sequencing (scRNA-seq), differential gene expression analysis, and Mendelian randomization (MR) to clarify the underlying genetic architecture of IDD. We identified 1,164 differentially expressed genes (DEGs) across four important cell types associated with IDD using publicly available single-cell datasets. A thorough gene network analysis identified 122 genes that may be connected to programmed cell death (PCD), a crucial route in the etiology of IDD. SLC40A1, PTGS2, and GABARAPL1 have been identified as noteworthy regulatory genes that may impede the advancement of IDD. Furthermore, distinct cellular subpopulations and dynamic gene expression patterns were revealed by functional enrichment analysis and pseudo-temporal ordering of chondrocytes. Our results highlight the therapeutic potential of GABARAPL1, PTGS2, and SLC40A1 targeting in the treatment of IDD.http://www.sciencedirect.com/science/article/pii/S2472630324001055Intervertebral disc degenerationProgrammed cell deathMendelian randomizationSingle cell analysis
spellingShingle Xuan Zhao
Qijun Wang
Shuaikang Wang
Wei Wang
Xiaolong Chen
Shibao Lu
A novel multi-omics approach for identifying key genes in intervertebral disc degeneration
SLAS Technology
Intervertebral disc degeneration
Programmed cell death
Mendelian randomization
Single cell analysis
title A novel multi-omics approach for identifying key genes in intervertebral disc degeneration
title_full A novel multi-omics approach for identifying key genes in intervertebral disc degeneration
title_fullStr A novel multi-omics approach for identifying key genes in intervertebral disc degeneration
title_full_unstemmed A novel multi-omics approach for identifying key genes in intervertebral disc degeneration
title_short A novel multi-omics approach for identifying key genes in intervertebral disc degeneration
title_sort novel multi omics approach for identifying key genes in intervertebral disc degeneration
topic Intervertebral disc degeneration
Programmed cell death
Mendelian randomization
Single cell analysis
url http://www.sciencedirect.com/science/article/pii/S2472630324001055
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