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人中性粒细胞在稳态和应激时的细胞和转录动态。

Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress.

机构信息

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.

Center for Omics Sciences (COSR), IRCCS San Raffaele Scientific Institute, Milan, Italy.

出版信息

Nat Immunol. 2022 Oct;23(10):1470-1483. doi: 10.1038/s41590-022-01311-1. Epub 2022 Sep 22.

DOI:10.1038/s41590-022-01311-1
PMID:36138183
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7615267/
Abstract

Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse; however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.

摘要

传统上被认为可塑性差的中性粒细胞，现在被认为具有功能多样性；然而，人类中性粒细胞异质性的程度和决定因素仍不清楚。我们对来自健康供体和接受生长因子暴露、造血干细胞（HSC-T）移植、胰腺癌发展和病毒感染的应激骨髓生成的患者的中性粒细胞进行了全面的免疫表型和转录组分析，在 bulk 和单细胞水平上进行了分析。我们发现体内人类中性粒细胞存在极高的多样性，反映了细胞动员、分化和暴露于环境信号的速度。发育和诱导转录程序的综合控制将灵活的粒细胞生成输出与刺激特异性功能反应的引发联系起来。在这种情况下，我们在接受 HSC-T 的患者的血液中检测到急性干扰素（IFN）反应，这与中性粒细胞中 IFN 刺激基因的显著上调相吻合，但单核细胞中没有。对人类中性粒细胞可塑性的系统表征可能会发现具有临床相关性的生物标志物，并支持诊断和治疗工具的开发。

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