IntroductionAplastic anemia (AA) is a bone marrow hematopoietic failure syndrome mediated by immune cells. The mechanism of this immune disorder is not well understood and therapeutic strategies still need to be improved.MethodsStudies have found that abnormalities in metabolisms promote the survival of AA cells. In recent years, an increasing number of studies have reported the immunosuppressive therapy for the treatment of AA. In this study, we analyzed the transcriptome of AA from peripheral blood compared with healthy donors by single-cell sequencing and identified the affected metabolic pathways including lysine degradation. We demonstrated that the metabolic abnormalities of T lymphocytes mainly focus on glycolysis/gluconeogenesis. In addition, the metabolic abnormalities of natural killer cells concentrated in oxidative phosphorylation.ResultsThe key genes involved in abnormal metabolic processes were Neustein neurotrophic factor (NENF), inositol polyphosphate-4-phosphatase type II B (INPP4B), aldo-keto reductase family 1, member C3 (AKR1C3), and carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 (CHST2) by differential gene expression analysis.DiscussionMolecule interaction analysis showed that tumor necrosis factor superfamily, member 12 (TNFSM12) in tumor necrosis factor (TNF) signaling was broadly activated in AA. In conclusion, we suppose that the treatment of the immune cells’ abnormal metabolic pathway may contribute to the development of novel strategies to treat AA.

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单细胞 RNA 测序描绘再生障碍性贫血儿童的代谢变化

简介再生障碍性贫血 (AA) 是由免疫细胞介导的骨髓造血功能衰竭综合征。这种免疫紊乱的机制尚不清楚，治疗策略仍有待改进。方法研究发现代谢异常促进AA细胞的存活。近年来，越来越多的研究报道了免疫抑制疗法治疗AA。在这项研究中，我们通过单细胞测序分析了与健康供体相比外周血 AA 的转录组，并确定了受影响的代谢途径，包括赖氨酸降解。我们证明了 T 淋巴细胞的代谢异常主要集中在糖酵解/糖异生上。此外，自然杀伤细胞的代谢异常集中在氧化磷酸化。NENF), 肌醇 polyphosphate-4-phosphatase type II B (INPP4B), 醛酮还原酶家族 1, 成员 C3 (AKR1C3), 和碳水化合物 (N-acetylglucosamine-6-O) 磺基转移酶 2 (CHST2) 通过差异基因表达分析。讨论分子相互作用分析表明，肿瘤坏死因子 (TNF) 信号转导中的肿瘤坏死因子超家族成员 12 (TNFSM12) 在 AA 中被广泛激活。总之，我们假设免疫细胞异常代谢途径的治疗可能有助于开发治疗 AA 的新策略。