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Gene regulatory network study of rheumatoid arthritis in single-cell chromatin landscapes of peripheral blood mononuclear cells

Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of rheumatoid arthritis (RA) at a single-cell resol...

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Main Authors: Zhang, Cantong (Author) , Hong, Xiaoping (Author) , Yu, Haiyan (Author) , Xu, Huixuan (Author) , Qiu, Xiaofen (Author) , Cai, Wanxia (Author) , Hocher, Berthold (Author) , Dai, Weier (Author) , Tang, Donge (Author) , Liu, Dongzhou (Author) , Dai, Yong (Author)
Format: Article (Journal)
Language:English
Published: July 2023
In: Modern rheumatology
Year: 2023, Volume: 33, Issue: 4, Pages: 739-750
ISSN:1439-7609
DOI:10.1093/mr/roac072
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/mr/roac072
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Author Notes:Cantong Zhang, Xiaoping Hong, Haiyan Yu, Huixuan Xu, Xiaofen Qiu, Wanxia Cai, Berthold Hocher, Weier Dai, Donge Tang, Dongzhou Liu, Yong Dai
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Summary:Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of rheumatoid arthritis (RA) at a single-cell resolution using epigenetic technology.Peripheral blood mononuclear cells of seven RA patients and seven natural controls were extracted nuclei suspensions for library construction. Subsequently, scATAC-seq was performed to generate a high-resolution map of active regulatory DNA for bioinformatics analysis.We obtained 22 accessible chromatin patterns. Then, 10 key TFs were involved in RA pathogenesis by regulating the activity of mitogen-activated protein kinase. Consequently, two genes (PTPRC and SPAG9) regulated by 10 key TFs were found, which may be associated with RA disease pathogenesis, and these TFs were obviously enriched in RA patients (P < .05, fold change value > 1.2). With further quantitative polymerase chain reaction validation on PTPRC and SPAG9 in monocytes, we found differential expression of these two genes, which were regulated by eight TFs [ZNF384, HNF1B, DMRTA2, MEF2A, NFE2L1, CREB3L4 (var. 2), FOSL2::JUNB (var. 2), and MEF2B], showing highly accessible binding sites in RA patients.These findings demonstrate the value of using scATAC-seq to reveal transcriptional regulatory variation in RA-derived peripheral blood mononuclear cells, providing insights into therapy from an epigenetic perspective.
Item Description:Artikel online veröffentlicht: 7. Juli 2022, korrigiert und gesetzt: 9. September 2022
Gesehen am 13.08.2024
Physical Description:Online Resource
ISSN:1439-7609
DOI:10.1093/mr/roac072

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