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Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro

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Published on: November 26, 2018

Monocytes differentiate along two alternative pathways during sterile inflammation.

Javiera Villar¹, Léa Ouaknin¹, Adeline Cros¹

¹Institut Curie, PSL Research University, INSERM, U932, Paris, France.

|May 16, 2023

Summary

Monocytes differentiate into macrophages (mo-Mac) or dendritic cells (mo-DC) during inflammation. This study reveals distinct pathways for mo-Mac and mo-DC differentiation, regulated by specific transcription factors like IRF1, ZNF366, and MAFF.

Keywords:

dendritic cells differentiation macrophages monocytes

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Published on: September 9, 2014

Area of Science:

Immunology
Cell Biology
Transcriptomics

Background:

Monocytes differentiate into macrophages (mo-Mac) and dendritic cells (mo-DC) in tissues during inflammation.
The precise differentiation pathways and potential continuum between mo-Mac and mo-DC populations are not fully understood.

Purpose of the Study:

To investigate whether mo-Mac and mo-DC arise from alternative differentiation pathways or a continuous process.
To identify key transcription factors governing monocyte fate commitment towards mo-Mac or mo-DC lineages.

Main Methods:

Temporal single-cell RNA sequencing in an in vitro human monocyte differentiation model.
In vivo validation using a mouse model of sterile peritonitis.
Computational analysis to identify candidate transcription factors.

Main Results:

Monocyte differentiation into mo-Mac and mo-DC follows divergent paths, with a fate decision occurring within 24 hours.
IRF1 is identified as a crucial transcription factor for mo-Mac differentiation, independent of interferon-stimulated gene regulation.
ZNF366 and MAFF are identified as key regulators for mo-DC development.

Conclusions:

Monocyte-derived macrophages and dendritic cells represent distinct cell fates.
Specific transcription factors, including IRF1, ZNF366, and MAFF, are essential for directing monocyte differentiation into alternative lineages.