The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution
ObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune disease, and various immune cells are involved in the initiation, progression, and regulation of SLE. Our goal was to reveal the chromatin accessibility landscape of peripheral blood mononuclear cells (PBMCs) in SLE patients at sing...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.641886/full |
| _version_ | 1818440533519892480 |
|---|---|
| author | Haiyan Yu Haiyan Yu Xiaoping Hong Hongwei Wu Fengping Zheng Zhipeng Zeng Weier Dai Lianghong Yin Dongzhou Liu Donge Tang Yong Dai |
| author_facet | Haiyan Yu Haiyan Yu Xiaoping Hong Hongwei Wu Fengping Zheng Zhipeng Zeng Weier Dai Lianghong Yin Dongzhou Liu Donge Tang Yong Dai |
| author_sort | Haiyan Yu |
| collection | DOAJ |
| description | ObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune disease, and various immune cells are involved in the initiation, progression, and regulation of SLE. Our goal was to reveal the chromatin accessibility landscape of peripheral blood mononuclear cells (PBMCs) in SLE patients at single-cell resolution and identify the transcription factors (TFs) that may drive abnormal immune responses.MethodsThe assay for transposase accessible chromatin in single-cell sequencing (scATAC-seq) method was applied to map the landscape of active regulatory DNA in immune cells from SLE patients at single-cell resolution, followed by clustering, peak annotation and motif analysis of PBMCs in SLE.ResultsPeripheral blood mononuclear cells were robustly clustered based on their types without using antibodies. We identified twenty patterns of TF activation that drive abnormal immune responses in SLE patients. Then, we observed ten genes that were highly associated with SLE pathogenesis by altering T cell activity. Finally, we found 12 key TFs regulating the above six genes (CD83, ELF4, ITPKB, RAB27A, RUNX3, and ZMIZ1) that may be related to SLE disease pathogenesis and were significantly enriched in SLE patients (p <0.05, FC >2). With qPCR experiments on CD83, ELF4, RUNX3, and ZMIZ1 in B cells, we observed a significant difference in the expression of genes (ELF4, RUNX3, and ZMIZ1), which were regulated by seven TFs (EWSR1-FLI1, MAF, MAFA, NFIB, NR2C2 (var. 2), TBX4, and TBX5). Meanwhile, the seven TFs showed highly accessible binding sites in SLE patients.ConclusionsThese results confirm the importance of using single-cell sequencing to uncover the real features of immune cells in SLE patients, reveal key TFs in SLE-PBMCs, and provide foundational insights relevant for epigenetic therapy. |
| first_indexed | 2024-12-14T18:13:52Z |
| format | Article |
| id | doaj.art-db44c9e4ab9d4763b135f3206ab722b1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T18:13:52Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-db44c9e4ab9d4763b135f3206ab722b12022-12-21T22:52:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.641886641886The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell ResolutionHaiyan Yu0Haiyan Yu1Xiaoping Hong2Hongwei Wu3Fengping Zheng4Zhipeng Zeng5Weier Dai6Lianghong Yin7Dongzhou Liu8Donge Tang9Yong Dai10Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaThe First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaDepartment of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaCollege of Natural Science, University of Texas at Austin, Austin, TX, United StatesDepartment of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune disease, and various immune cells are involved in the initiation, progression, and regulation of SLE. Our goal was to reveal the chromatin accessibility landscape of peripheral blood mononuclear cells (PBMCs) in SLE patients at single-cell resolution and identify the transcription factors (TFs) that may drive abnormal immune responses.MethodsThe assay for transposase accessible chromatin in single-cell sequencing (scATAC-seq) method was applied to map the landscape of active regulatory DNA in immune cells from SLE patients at single-cell resolution, followed by clustering, peak annotation and motif analysis of PBMCs in SLE.ResultsPeripheral blood mononuclear cells were robustly clustered based on their types without using antibodies. We identified twenty patterns of TF activation that drive abnormal immune responses in SLE patients. Then, we observed ten genes that were highly associated with SLE pathogenesis by altering T cell activity. Finally, we found 12 key TFs regulating the above six genes (CD83, ELF4, ITPKB, RAB27A, RUNX3, and ZMIZ1) that may be related to SLE disease pathogenesis and were significantly enriched in SLE patients (p <0.05, FC >2). With qPCR experiments on CD83, ELF4, RUNX3, and ZMIZ1 in B cells, we observed a significant difference in the expression of genes (ELF4, RUNX3, and ZMIZ1), which were regulated by seven TFs (EWSR1-FLI1, MAF, MAFA, NFIB, NR2C2 (var. 2), TBX4, and TBX5). Meanwhile, the seven TFs showed highly accessible binding sites in SLE patients.ConclusionsThese results confirm the importance of using single-cell sequencing to uncover the real features of immune cells in SLE patients, reveal key TFs in SLE-PBMCs, and provide foundational insights relevant for epigenetic therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2021.641886/fullsystemic lupus erythematosussingle-cell chromatin accessible assayperipheral blood mononuclear cellstranscription factormarker |
| spellingShingle | Haiyan Yu Haiyan Yu Xiaoping Hong Hongwei Wu Fengping Zheng Zhipeng Zeng Weier Dai Lianghong Yin Dongzhou Liu Donge Tang Yong Dai The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution Frontiers in Immunology systemic lupus erythematosus single-cell chromatin accessible assay peripheral blood mononuclear cells transcription factor marker |
| title | The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution |
| title_full | The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution |
| title_fullStr | The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution |
| title_full_unstemmed | The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution |
| title_short | The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution |
| title_sort | chromatin accessibility landscape of peripheral blood mononuclear cells in patients with systemic lupus erythematosus at single cell resolution |
| topic | systemic lupus erythematosus single-cell chromatin accessible assay peripheral blood mononuclear cells transcription factor marker |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.641886/full |
| work_keys_str_mv | AT haiyanyu thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT haiyanyu thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT xiaopinghong thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT hongweiwu thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT fengpingzheng thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT zhipengzeng thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT weierdai thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT lianghongyin thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT dongzhouliu thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT dongetang thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT yongdai thechromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT haiyanyu chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT haiyanyu chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT xiaopinghong chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT hongweiwu chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT fengpingzheng chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT zhipengzeng chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT weierdai chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT lianghongyin chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT dongzhouliu chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT dongetang chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution AT yongdai chromatinaccessibilitylandscapeofperipheralbloodmononuclearcellsinpatientswithsystemiclupuserythematosusatsinglecellresolution |