AUTHOR=Perik-Zavodskii Roman , Perik-Zavodskaia Olga , Alrhmoun Saleh , Volynets Marina , Shevchenko Julia , Nazarov Kirill , Denisova Vera , Sennikov Sergey 

TITLE=Single-cell multi-omics reveal stage of differentiation and trajectory-dependent immunity-related gene expression patterns in human erythroid cells

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1431303

DOI=10.3389/fimmu.2024.1431303

ISSN=1664-3224

ABSTRACT=<p>The role of Erythroid cells in immune regulation and immunosuppression is one of the emerging topics in modern immunology that still requires further clarification as Erythroid cells from different tissues and different species express different immunoregulatory molecules. In this study, we performed a thorough investigation of human bone marrow Erythroid cells from adult healthy donors and adult acute lymphoblastic leukemia patients using the state-of-the-art single-cell targeted proteomics and transcriptomics via BD Rhapsody and cancer-related gene copy number variation analysis via NanoString Sprint Profiler. We found that human bone marrow Erythroid cells express the <italic>ARG1, LGALS1, LGALS3, LGALS9</italic>, and <italic>C10orf54</italic> (VISTA) immunosuppressive genes, <italic>CXCL5, CXCL8</italic>, and <italic>VEGFA</italic> cytokine genes, as well as the genes involved in antimicrobial immunity and MHC Class II antigen presentation. We also found that <italic>ARG1</italic> gene expression was restricted to the single erythroid cell cluster that we termed ARG1-positive Orthochromatic erythroblasts and that late Erythroid cells lose <italic>S100A9</italic> and gain <italic>MZB1</italic> gene expression in case of acute lymphoblastic leukemia. These findings show that steady-state erythropoiesis bone marrow Erythroid cells express myeloid signature genes even without any transdifferentiating stimulus like cancer.</p>