What question did this study set out to answer?

To establish a stable, self-replicating ex vivo culture system for alveolar macrophages capable of supporting high-throughput functional genetic investigations.

December 13, 2021Open Access

FLAMs: A self-replicating ex vivo model of alveolar macrophages for functional genetic studies

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Authors

STSean M. ThomasMichigan State University KWKathryn A. WierengaUtrecht University JPJames J. PestkaMichigan State University

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Implication

In vitro study demonstrates a self-replicating alveolar macrophage model, enabling high-throughput functional genetic screening.

Key Points

To establish a stable, self-replicating ex vivo culture system for alveolar macrophages capable of supporting high-throughput functional genetic investigations.
Generated fetal liver-derived alveolar-like macrophages (FLAMs) using cytokine supplementation with GM-CSF and TGF-beta.
Conducted CRISPR-Cas9 targeted disruption of Marco and Il1r1 to assess cellular responses to crystalline silica.
Performed a genome-wide CRISPR-Cas9 knockout screen to identify genes regulating cell-surface expression of the alveolar macrophage marker Siglec-F.
FLAMs maintained native alveolar macrophage morphology, marker expression, and functional properties across extended culture periods.
Targeted editing confirmed that loss of Marco and Il1r1 directly modulates macrophage inflammatory responses to crystalline silica.
Genome-wide knockout screening identified previously unknown regulators of Siglec-F expression, highlighting critical roles for peroxisomal pathway genes.

Cite This Study

Thomas et al. (2021) studied this question.

synapsesocial.com/papers/6aa0489e65b620ad82cd7276 https://doi.org/10.1101/2021.12.12.472259

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FLAMs: A self-replicating ex vivo model of alveolar macrophages for functional genetic studies

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Key Points

Cite This Study

FLAMs: A self-replicating ex vivo model of alveolar macrophages for functional genetic studies

Discussion

Member takes

Implication

Key Points

Cite This Study

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