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单细胞多组学揭示人类红细胞分化阶段和轨迹相关免疫相关基因表达模式。

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

机构信息

Laboratory of molecular immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.

Clinic of immunopathology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia.

出版信息

Front Immunol. 2024 Aug 29;15:1431303. doi: 10.3389/fimmu.2024.1431303. eCollection 2024.

DOI:10.3389/fimmu.2024.1431303
PMID:39267736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11390661/
Abstract

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 , and (VISTA) immunosuppressive genes, , and cytokine genes, as well as the genes involved in antimicrobial immunity and MHC Class II antigen presentation. We also found that gene expression was restricted to the single erythroid cell cluster that we termed ARG1-positive Orthochromatic erythroblasts and that late Erythroid cells lose and gain 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.

摘要

红细胞在免疫调节和免疫抑制中的作用是现代免疫学中一个新兴的课题,仍需要进一步阐明,因为不同组织和不同物种的红细胞表达不同的免疫调节分子。在这项研究中,我们使用最先进的单细胞靶向蛋白质组学和转录组学(通过 BD Rhapsody)以及通过 NanoString Sprint Profiler 进行癌症相关基因拷贝数变异分析,对来自成年健康供体和成人急性淋巴细胞白血病患者的人骨髓红细胞进行了全面研究。我们发现人骨髓红细胞表达、和(VISTA)免疫抑制基因、、和细胞因子基因,以及参与抗菌免疫和 MHC Ⅱ类抗原呈递的基因。我们还发现基因表达仅限于我们称为 ARG1 阳性正染红细胞的单个红细胞簇,并且在急性淋巴细胞白血病的情况下,晚期红细胞失去表达和获得基因表达。这些发现表明,静止状态下的红细胞生成骨髓红细胞表达髓样特征基因,即使没有任何像癌症这样的转分化刺激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/512e3441deb4/fimmu-15-1431303-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/e4960452a623/fimmu-15-1431303-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/ba79c743c227/fimmu-15-1431303-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/7b94455b6906/fimmu-15-1431303-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/6af09d631623/fimmu-15-1431303-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/512e3441deb4/fimmu-15-1431303-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/e4960452a623/fimmu-15-1431303-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/ba79c743c227/fimmu-15-1431303-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/7b94455b6906/fimmu-15-1431303-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/6af09d631623/fimmu-15-1431303-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e0/11390661/512e3441deb4/fimmu-15-1431303-g005.jpg

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