Single-cell transcriptomics reveals phenotypic and functional alterations of erythroid progenitor cells in tuberculosis patients

IF 2.9 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2026-03-01 Epub Date: 2026-02-16 DOI:10.1016/j.tube.2026.102746

Hao Zhang , Yan Cao , Ling Yang , Bowen Liu , Jingzhi Guan , Xinjing Wang

{"title":"Single-cell transcriptomics reveals phenotypic and functional alterations of erythroid progenitor cells in tuberculosis patients","authors":"Hao Zhang , Yan Cao , Ling Yang , Bowen Liu , Jingzhi Guan , Xinjing Wang","doi":"10.1016/j.tube.2026.102746","DOIUrl":null,"url":null,"abstract":"<div><div>Anemia is a common complication of tuberculosis (TB), closely associated with impaired host immune function and poor prognosis; however, its impact on the dynamic alterations of erythroid progenitor cells (EPCs) remains largely unexplored. In this study, we integrated and analyzed single-cell transcriptomic data from peripheral blood mononuclear cells (PBMC) of healthy controls, latent tuberculosis (LTB), TB, and disseminated tuberculosis (DTB) cohorts, as well as 18F-FDG-labeled TB lung tissues and adjacent uninvolved regions. At single-cell resolution, we identified ten EPCs clusters within PBMC, among which clusters 2–6 represented DTB-specific subpopulations (EPC_DTB). These EPC_DTB exhibited metabolic reprogramming (including glycolysis, arginine, and lipid metabolism) accompanied by upregulation of IFITM3/JUN and ribosomal genes, consistent with enhanced differentiation. EPC_DTB and EPC_TB interacted with macrophages, dendritic cells, and monocytes through the ANNEXIN and GALECTIN signaling pathways, while these immune cells reciprocally regulated EPCs subsets via the MIF signaling axis. In lung tissues, EPCs (12 clusters) displayed disease-specific characteristics, with clusters 0, 3, and 6 uniquely present in TB lesions. The EPC_High subpopulation within inflammatory foci showed significant upregulation of GZMA, IL32, CCL5, and CHI3L1, whereas EPC_Low communicated with immune cells, epithelial cells, and stromal cells through the MDK–NCL signaling pathway. Moreover, we established an LTB predictive model based on EPC_LTB signature genes in PBMC (GRIK3, S100B, ZDHHC19, and LRRN3). Our study uncovers the heterogeneity of EPCs across different TB stages and tissue compartments, delineates their bidirectional crosstalk with immune cells, and establishes a link among anemia, immune regulation, and EPCs biology, thereby proposing potential diagnostic biomarkers and therapeutic targets.</div></div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"157 ","pages":"Article 102746"},"PeriodicalIF":2.9000,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tuberculosis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1472979226000168","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/2/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Anemia is a common complication of tuberculosis (TB), closely associated with impaired host immune function and poor prognosis; however, its impact on the dynamic alterations of erythroid progenitor cells (EPCs) remains largely unexplored. In this study, we integrated and analyzed single-cell transcriptomic data from peripheral blood mononuclear cells (PBMC) of healthy controls, latent tuberculosis (LTB), TB, and disseminated tuberculosis (DTB) cohorts, as well as 18F-FDG-labeled TB lung tissues and adjacent uninvolved regions. At single-cell resolution, we identified ten EPCs clusters within PBMC, among which clusters 2–6 represented DTB-specific subpopulations (EPC_DTB). These EPC_DTB exhibited metabolic reprogramming (including glycolysis, arginine, and lipid metabolism) accompanied by upregulation of IFITM3/JUN and ribosomal genes, consistent with enhanced differentiation. EPC_DTB and EPC_TB interacted with macrophages, dendritic cells, and monocytes through the ANNEXIN and GALECTIN signaling pathways, while these immune cells reciprocally regulated EPCs subsets via the MIF signaling axis. In lung tissues, EPCs (12 clusters) displayed disease-specific characteristics, with clusters 0, 3, and 6 uniquely present in TB lesions. The EPC_High subpopulation within inflammatory foci showed significant upregulation of GZMA, IL32, CCL5, and CHI3L1, whereas EPC_Low communicated with immune cells, epithelial cells, and stromal cells through the MDK–NCL signaling pathway. Moreover, we established an LTB predictive model based on EPC_LTB signature genes in PBMC (GRIK3, S100B, ZDHHC19, and LRRN3). Our study uncovers the heterogeneity of EPCs across different TB stages and tissue compartments, delineates their bidirectional crosstalk with immune cells, and establishes a link among anemia, immune regulation, and EPCs biology, thereby proposing potential diagnostic biomarkers and therapeutic targets.

查看原文本刊更多论文

单细胞转录组学揭示了结核病患者红系祖细胞的表型和功能改变。

贫血是结核病（TB）的常见并发症，与宿主免疫功能受损和预后不良密切相关；然而，其对红系祖细胞（EPCs）动态改变的影响在很大程度上仍未被探索。在这项研究中，我们整合并分析了来自健康对照组、潜伏性结核病（LTB）、结核病和弥散性结核病（DTB）队列以及18f - fdg标记的结核病肺组织和邻近未累及区域的外周血单核细胞（PBMC）的单细胞转录组学数据。在单细胞分辨率下，我们在PBMC中鉴定了10个EPCs集群，其中集群2-6代表dtb特异性亚群（EPC_DTB）。这些EPC_DTB表现出代谢重编程（包括糖酵解、精氨酸和脂质代谢），并伴有IFITM3/JUN和核糖体基因的上调，与分化增强相一致。EPC_DTB和EPC_TB通过ANNEXIN和GALECTIN信号通路与巨噬细胞、树突状细胞和单核细胞相互作用，而这些免疫细胞通过MIF信号轴相互调节EPCs亚群。在肺组织中，EPCs（12簇）显示出疾病特异性特征，簇0、3和6仅存在于结核病病变中。炎症灶内的EPC_High亚群显示GZMA、IL32、CCL5和CHI3L1的显著上调，而EPC_Low则通过MDK-NCL信号通路与免疫细胞、上皮细胞和基质细胞进行交流。此外，我们还建立了基于PBMC EPC_LTB特征基因（GRIK3、S100B、ZDHHC19和LRRN3）的LTB预测模型。我们的研究揭示了EPCs在不同结核分期和组织区室中的异质性，描绘了它们与免疫细胞的双向串扰，并建立了贫血、免疫调节和EPCs生物学之间的联系，从而提出了潜在的诊断生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.