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Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics.

ABSTRACT: Monocytes continuously adapt their shapes for proper circulation and elicitation of effective immune responses. Although these functions depend on the cell mechanical properties, the mechanical behavior of monocytes is still poorly understood and accurate physiologically relevant data on basic mechanical properties are lacking almost entirely. By combining several complementary single-cell force spectroscopy techniques, we report that the mechanical properties of human monocyte are strain-rate dependent, and that chemokines can induce alterations in viscoelastic behavior. In addition, our findings indicate that human monocytes are heterogeneous mechanically and this heterogeneity is regulated by chemokine CCL2. The technology presented here can be readily used to reveal mechanical complexity of the blood cell population in disease conditions, where viscoelastic properties may serve as physical biomarkers for disease progression and response to therapy.

SUBMITTER: Evers TMJ

PROVIDER: S-EPMC8693412 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics.

Evers Tom M J TMJ Sheikhhassani Vahid V Haks Mariëlle C MC Storm Cornelis C Ottenhoff Tom H M THM Mashaghi Alireza A

iScience 20211202 1

Monocytes continuously adapt their shapes for proper circulation and elicitation of effective immune responses. Although these functions depend on the cell mechanical properties, the mechanical behavior of monocytes is still poorly understood and accurate physiologically relevant data on basic mechanical properties are lacking almost entirely. By combining several complementary single-cell force spectroscopy techniques, we report that the mechanical properties of human monocyte are strain-rate d ...[more]

PMID: 34988399

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Project description:BackgroundIn tuberculosis (TB) infection, monocytes play a crucial role in regulating the balance between immune tolerance and immune response through various mechanisms. A deeper understanding of the roles of monocyte subsets in TB immune responses may facilitate the development of novel immunotherapeutic strategies and improve TB prevention and treatment.MethodsWe retrieved and processed raw single-cell RNA-seq data from SRP247583. Single-cell RNA-seq combined with bioinformatics analysis was employed to investigate the roles of monocytes in TB progression.ResultsOur findings revealed that classical monocytes expressing inflammatory mediators increased as the disease progressed, whereas non-classical monocytes expressing molecules associated with anti-pathogen infection were progressively depleted. Pseudotime analysis delineated the differentiation trajectory of monocytes from classical to intermediate to non-classical subsets. An abnormal differentiation trajectory to non-classical monocytes may represent a key mechanism underlying TB pathogenesis, with CEBPB and CORO1A identified as genes potentially related to TB development. Analysis of key transcription factors in non-classical monocytes indicated that IRF9 was the only downregulated transcription factor with high AUC activity in this subset. The expression of IRF9 exhibited a decreasing trend in both latent TB infection (LTBI) and active TB groups. Furthermore, dysregulation of transcription factor regulatory networks appeared to impair ferroptosis, with ferroptosis-associated genes MEF2C, MICU1, and PRR5 identified as potential targets of IRF9. Through cell communication analysis, we found that interactions between non-classical monocytes and other subpopulations may mediate TB progression, with MIF and LGALS9 highlighted as potential signaling pathways.ConclusionThis study employs bioinformatics analysis in conjunction with single-cell sequencing technology to uncover the crucial role of monocyte subsets in tuberculosis infection.

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Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics.

Publications

Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics.

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