AUTHOR=Yu Haiyan , Hong Xiaoping , Wu Hongwei , Zheng Fengping , Zeng Zhipeng , Dai Weier , Yin Lianghong , Liu Dongzhou , Tang Donge , Dai Yong 

TITLE=The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.641886

DOI=10.3389/fimmu.2021.641886

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>Systemic 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.</p></sec><sec><title>Methods</title><p>The 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.</p></sec><sec><title>Results</title><p>Peripheral 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 (<italic>CD83</italic>, <italic>ELF4</italic>, <italic>ITPKB</italic>, <italic>RAB27A</italic>, <italic>RUNX3</italic>, and <italic>ZMIZ1</italic>) that may be related to SLE disease pathogenesis and were significantly enriched in SLE patients (p &lt;0.05, FC &gt;2). With qPCR experiments on <italic>CD83</italic>, <italic>ELF4</italic>, <italic>RUNX3</italic>, and <italic>ZMIZ1</italic> in B cells, we observed a significant difference in the expression of genes (<italic>ELF4</italic>, <italic>RUNX3</italic>, and <italic>ZMIZ1</italic>), 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.</p></sec><sec><title>Conclusions</title><p>These 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.</p></sec>