New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis
Abstract Background Synpolydactyly (SPD) is mainly caused by mutations of polyalanine expansion (PAE) in the transcription factor gene HOXD13 and the involved cell types and signal pathway are still not clear possible pathways and single-cell expression characteristics of limb bud in HOXD13 PAE mice...
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| Language: | English |
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BMC
2024-10-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-024-01974-9 |
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| author | Xiumin Chen Xiaofang Shen Tao Yang Yixuan Cao Xiuli Zhao |
| author_facet | Xiumin Chen Xiaofang Shen Tao Yang Yixuan Cao Xiuli Zhao |
| author_sort | Xiumin Chen |
| collection | DOAJ |
| description | Abstract Background Synpolydactyly (SPD) is mainly caused by mutations of polyalanine expansion (PAE) in the transcription factor gene HOXD13 and the involved cell types and signal pathway are still not clear possible pathways and single-cell expression characteristics of limb bud in HOXD13 PAE mice was analyzed in this study. Method We investigated a previous study of a mouse model with SPD and conducted weighted gene co-expression network analysis (WGCNA) using a single-cell RNA sequencing dataset from limb bud cells of SPD mouse model of HOXD13 + 7A heterozygote. Results Analysis of WGCNA revealed that synpolydactyly-associated Hoxd13 PAEs alter the immune response and osteoclast differentiation, and enhance DNA replication. Bmp4, Hand2, Hoxd12, Lnp, Prrx1, Gmnn, and Cdc6 were found to play potentially key roles in synpolydactyly. Conclusions These findings evaluated the main genes related to SPD with PAE mutations in HOXD13 and advance our understanding of human limb development. |
| format | Article |
| id | doaj-art-8825d8e27a1e4c4e8a9c59bb2fc406e6 |
| institution | OA Journals |
| issn | 1755-8794 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj-art-8825d8e27a1e4c4e8a9c59bb2fc406e62025-08-20T02:18:25ZengBMCBMC Medical Genomics1755-87942024-10-011711810.1186/s12920-024-01974-9New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysisXiumin Chen0Xiaofang Shen1Tao Yang2Yixuan Cao3Xiuli Zhao4McKusick-Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical CollegePediatric Orthopedics, Children’s Hospital of Soochow UniversityMcKusick-Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical CollegeMcKusick-Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical CollegeMcKusick-Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical CollegeAbstract Background Synpolydactyly (SPD) is mainly caused by mutations of polyalanine expansion (PAE) in the transcription factor gene HOXD13 and the involved cell types and signal pathway are still not clear possible pathways and single-cell expression characteristics of limb bud in HOXD13 PAE mice was analyzed in this study. Method We investigated a previous study of a mouse model with SPD and conducted weighted gene co-expression network analysis (WGCNA) using a single-cell RNA sequencing dataset from limb bud cells of SPD mouse model of HOXD13 + 7A heterozygote. Results Analysis of WGCNA revealed that synpolydactyly-associated Hoxd13 PAEs alter the immune response and osteoclast differentiation, and enhance DNA replication. Bmp4, Hand2, Hoxd12, Lnp, Prrx1, Gmnn, and Cdc6 were found to play potentially key roles in synpolydactyly. Conclusions These findings evaluated the main genes related to SPD with PAE mutations in HOXD13 and advance our understanding of human limb development.https://doi.org/10.1186/s12920-024-01974-9SynpolydactylyHOXD13Polyalanine expansionSingle-cell RNA sequencingImmune response |
| spellingShingle | Xiumin Chen Xiaofang Shen Tao Yang Yixuan Cao Xiuli Zhao New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis BMC Medical Genomics Synpolydactyly HOXD13 Polyalanine expansion Single-cell RNA sequencing Immune response |
| title | New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis |
| title_full | New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis |
| title_fullStr | New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis |
| title_full_unstemmed | New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis |
| title_short | New insight into the development of synpolydactyly caused by expansion of HOXD13 polyalanine based on weighted gene co-expression network analysis |
| title_sort | new insight into the development of synpolydactyly caused by expansion of hoxd13 polyalanine based on weighted gene co expression network analysis |
| topic | Synpolydactyly HOXD13 Polyalanine expansion Single-cell RNA sequencing Immune response |
| url | https://doi.org/10.1186/s12920-024-01974-9 |
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