Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells

Florian Wimmers; Nikita Subedi; Nicole van Buuringen; Daan Heister; Judith Vivié; Inge Beeren-Reinieren; Rob Woestenenk; Harry Dolstra; Aigars Piruska; Joannes F M Jacobs; Alexander van Oudenaarden; Carl G Figdor; Wilhelm T S Huck; I Jolanda M de Vries; Jurjen Tel

doi:10.1038/s41467-018-05784-3

Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells

Florian Wimmers, Nikita Subedi, Nicole van Buuringen, Daan Heister, Judith Vivié, Inge Beeren-Reinieren, Rob Woestenenk, Harry Dolstra, Aigars Piruska, Joannes F M Jacobs, Alexander van Oudenaarden, Carl G Figdor, Wilhelm T S Huck, I Jolanda M de Vries, Jurjen Tel

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

102 Citaten (Scopus)

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Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNFα production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. By modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.

Originele taal-2	Engels
Pagina's (van-tot)	3317
Tijdschrift	Nature Communications
Volume	9
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-018-05784-3
Status	Gepubliceerd - 20 aug. 2018

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Wimmers, F., Subedi, N., van Buuringen, N., Heister, D., Vivié, J., Beeren-Reinieren, I., Woestenenk, R., Dolstra, H., Piruska, A., Jacobs, J. F. M., van Oudenaarden, A., Figdor, C. G., Huck, W. T. S., de Vries, I. J. M., & Tel, J. (2018). Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nature Communications, 9(1), 3317. https://doi.org/10.1038/s41467-018-05784-3

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title = "Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells",

abstract = "Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNFα production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. By modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.",

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author = "Florian Wimmers and Nikita Subedi and {van Buuringen}, Nicole and Daan Heister and Judith Vivi{\'e} and Inge Beeren-Reinieren and Rob Woestenenk and Harry Dolstra and Aigars Piruska and Jacobs, {Joannes F M} and {van Oudenaarden}, Alexander and Figdor, {Carl G} and Huck, {Wilhelm T S} and {de Vries}, {I Jolanda M} and Jurjen Tel",

year = "2018",

month = aug,

day = "20",

doi = "10.1038/s41467-018-05784-3",

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Wimmers, F, Subedi, N, van Buuringen, N, Heister, D, Vivié, J, Beeren-Reinieren, I, Woestenenk, R, Dolstra, H, Piruska, A, Jacobs, JFM, van Oudenaarden, A, Figdor, CG, Huck, WTS, de Vries, IJM & Tel, J 2018, 'Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells', Nature Communications, vol. 9, nr. 1, blz. 3317. https://doi.org/10.1038/s41467-018-05784-3

Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. / Wimmers, Florian; Subedi, Nikita; van Buuringen, Nicole et al.
In: Nature Communications, Vol. 9, Nr. 1, 20.08.2018, blz. 3317.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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T1 - Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells

AU - Wimmers, Florian

AU - Subedi, Nikita

AU - van Buuringen, Nicole

AU - Heister, Daan

AU - Vivié, Judith

AU - Beeren-Reinieren, Inge

AU - Woestenenk, Rob

AU - Dolstra, Harry

AU - Piruska, Aigars

AU - Jacobs, Joannes F M

AU - van Oudenaarden, Alexander

AU - Figdor, Carl G

AU - Huck, Wilhelm T S

AU - de Vries, I Jolanda M

AU - Tel, Jurjen

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N2 - Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNFα production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. By modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.

AB - Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNFα production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. By modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.

KW - Cellular Microenvironment

KW - Cross-Priming

KW - Dendritic Cells/metabolism

KW - Gene Expression Regulation

KW - Humans

KW - Interferon Type I/biosynthesis

KW - Jurkat Cells

KW - Paracrine Communication

KW - Sequence Analysis, RNA

KW - Single-Cell Analysis/methods

KW - Stochastic Processes

KW - Toll-Like Receptors/metabolism

U2 - 10.1038/s41467-018-05784-3

DO - 10.1038/s41467-018-05784-3

M3 - Article

C2 - 30127440

SN - 2041-1723

VL - 9

SP - 3317

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells

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