Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis

ObjectiveGenetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot.MethodsWe integrated single-cell assaying transposase-accessible chromatin sequencing (scA...

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Autores principales:	Huixuan Xu, Haiyan Yu, Lixiong Liu, Hongwei Wu, Cantong Zhang, Wanxia Cai, Xiaoping Hong, Dongzhou Liu, Donge Tang, Yong Dai
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ankylosing spondylitis single-cell RNA sequencing single-cell assaying transposase accessible chromatin sequencing NFkB TNF signaling pathway Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/02b38754374c4765b29df074b937e432
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spelling	oai:doaj.org-article:02b38754374c4765b29df074b937e4322021-11-22T12:13:11ZIntegrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis1664-322410.3389/fimmu.2021.760381https://doaj.org/article/02b38754374c4765b29df074b937e4322021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.760381/fullhttps://doaj.org/toc/1664-3224ObjectiveGenetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot.MethodsWe integrated single-cell assaying transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to explore the key genes and related mechanisms associated with AS pathogenesis.ResultsWe identified 18 cell types in peripheral mononuclear cells from patients with AS and normal controls and summarized the cell-type-specific abnormal genes by scRNA-seq. Interestingly, we found that the pathogenic gene NFKB involved in AS progression originated from CD8+ T cells. Moreover, we observed an abnormal tumor TNF pathway mediated by abnormal expression of TNF, NFKB, FOS, JUN, and JUNB, and scATAC-seq results confirmed the abnormal accessible binding sites of transcriptional factors FOS, JUN, and JUNB. The final magnetic bead sorting and quantitative real-time PCR(RT-qPCR) confirmed that NFKB, FOS, JUN, and JUNB in CD8+ T cells differed in the AS group.ConclusionsOur results revealed a possible mechanism by which NFKB abnormally regulates FOS, JUN, and JUNB and drives AS progression, providing a novel perspective from a single cell point of view in AS.Huixuan XuHaiyan YuLixiong LiuHongwei WuCantong ZhangWanxia CaiXiaoping HongDongzhou LiuDonge TangYong DaiYong DaiFrontiers Media S.A.articleankylosing spondylitissingle-cell RNA sequencingsingle-cell assaying transposase accessible chromatin sequencingNFkBTNF signaling pathwayImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ankylosing spondylitis single-cell RNA sequencing single-cell assaying transposase accessible chromatin sequencing NFkB TNF signaling pathway Immunologic diseases. Allergy RC581-607
spellingShingle	ankylosing spondylitis single-cell RNA sequencing single-cell assaying transposase accessible chromatin sequencing NFkB TNF signaling pathway Immunologic diseases. Allergy RC581-607 Huixuan Xu Haiyan Yu Lixiong Liu Hongwei Wu Cantong Zhang Wanxia Cai Xiaoping Hong Dongzhou Liu Donge Tang Yong Dai Yong Dai Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis
description	ObjectiveGenetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot.MethodsWe integrated single-cell assaying transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to explore the key genes and related mechanisms associated with AS pathogenesis.ResultsWe identified 18 cell types in peripheral mononuclear cells from patients with AS and normal controls and summarized the cell-type-specific abnormal genes by scRNA-seq. Interestingly, we found that the pathogenic gene NFKB involved in AS progression originated from CD8+ T cells. Moreover, we observed an abnormal tumor TNF pathway mediated by abnormal expression of TNF, NFKB, FOS, JUN, and JUNB, and scATAC-seq results confirmed the abnormal accessible binding sites of transcriptional factors FOS, JUN, and JUNB. The final magnetic bead sorting and quantitative real-time PCR(RT-qPCR) confirmed that NFKB, FOS, JUN, and JUNB in CD8+ T cells differed in the AS group.ConclusionsOur results revealed a possible mechanism by which NFKB abnormally regulates FOS, JUN, and JUNB and drives AS progression, providing a novel perspective from a single cell point of view in AS.
format	article
author	Huixuan Xu Haiyan Yu Lixiong Liu Hongwei Wu Cantong Zhang Wanxia Cai Xiaoping Hong Dongzhou Liu Donge Tang Yong Dai Yong Dai
author_facet	Huixuan Xu Haiyan Yu Lixiong Liu Hongwei Wu Cantong Zhang Wanxia Cai Xiaoping Hong Dongzhou Liu Donge Tang Yong Dai Yong Dai
author_sort	Huixuan Xu
title	Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis
title_short	Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis
title_full	Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis
title_fullStr	Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis
title_full_unstemmed	Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis
title_sort	integrative single-cell rna-seq and atac-seq analysis of peripheral mononuclear cells in patients with ankylosing spondylitis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/02b38754374c4765b29df074b937e432
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Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis

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