Macrophages are able to coordinate immune responses to inflammatory conditions, tumors and degenerative disorders. Although major polarization regulatory elements have been identified, macrophages in vivo may present more complex transcriptional signatures. Gene regulatory networks provide a powerful framework for studying macrophage polarization comprehensively. It's a good source for the discovery of key regulators for macrophage reprogramming. Combining deep, industry-leading expertise with an innovative macrophage therapeutics development platform, Creative Biolabs has constructed a logical model of gene regulatory networks to understand how they affect macrophage polarization, and we offer high-quality macrophage reprogramming services.

Gene Regulatory Networks Facilitate Macrophage Reprogramming

Computational models of gene regulatory networks are good approaches to study how cells integrate several signals driving the cell phenotypic changes, especially for their ability to quantitatively and qualitatively describe a great variety of poorly characterized biological situations. In recent years, gene regulatory networks are of particular interest in macrophages.

Fig.1 Macrophage reprogramming as a potential target between tumor associated macrophages (TAMs) and CD8-positive (CD8+) T cells.^1,2

• Gene regulatory network models have revealed key transcription factors that control macrophage polarization, including E2F1, MYC, PPARγ, and STAT6. These regulators are essential for maintaining specific macrophage phenotypes and represent potential targets for therapeutic reprogramming.
• Gene regulatory network analysis has uncovered two significant metabolic switches during macrophage polarization. M1 macrophages primarily utilize anaerobic glycolysis, with upregulation of genes involved in the Warburg effect. M2 macrophages show increased biosynthesis of inosine monophosphate and enhanced oxidative phosphorylation.
• Gene regulatory networks integrate multiple signaling pathways and provide insights into how macrophages respond to various stimuli, leading to distinct polarization states such as M1, M2a, M2b, and M2c.

Reprogramming Macrophages by Gene Regulatory Networks at Creative Biolabs

To obtain a broader overview of the gene regulatory networks that drive macrophage polarization and the heterogeneous single-cell subpopulations in the process, bulk RNA-seq/single-cell RNA-seq and ATAC-seq assays are usually performed to obtain a comprehensive macrophage transcription profile. Our seasoned scientists integrate all the data to construct a logical network model for the gene regulation driving macrophage polarization to the M1, M2a, M2b, and M2c phenotypes.

With an experienced team of in-house macrophage reprogramming experts, Creative Biolabs is proud to share our experience in developing highly customizable solutions for our customers. For more detailed information, please feel free to contact us and further discuss with our scientists.

Related Products

Macrophages play a critical role in the immune system, and their functions and phenotypes can be reprogrammed through gene regulatory networks that enable the modulation of pro- or anti-inflammatory responses. In the laboratory, synthetic biology methods are widely used to quantitatively study gene regulatory networks. For example, by constructing synthetic gene circuits, it is possible to precisely control the expression of target genes and explore the impact of transcriptional memory phenomena on macrophage function.

To support related research, we offer the following scientific products to help researchers realize gene editing, phenotyping and functional validation of macrophages.

Service Features

Personalized Programs

According to the specific needs and research objectives of our clients, we are able to customize personalized gene regulatory network protocols for precise reprogramming.

Multiple Reprogramming Strategies

We provide different gene combinations and regulatory strategies to help researchers explore the functions of macrophages in different pathological states.

Latest Research Results

Utilizing the latest scientific research and technology platforms to ensure our services are at the forefront of the field.

High-throughput Screening

High-throughput technology is used to quickly screen the best gene combinations and improve experimental efficiency.

Experienced Research Team

Our team consists of experts in the fields of biology, genomics and bioinformatics, with rich theoretical and practical experience.

Continuous Technical Support

We provide a full range of technical support and consulting services from project design to result analysis to ensure the smooth progress of the project.

Publications

Franziska Hörhold et al. investigated the gene regulation of metabolism in order to better understand the processes that regulate M1/M2 polarization and identified essential regulators in M2-like macrophages, providing a possible starting point for transforming M2-like macrophages into M1-like macrophages.

Fig. 2 The impact of the predicted regulators on metabolic and M1/M2 associated genes was investigated on a large scale by profiling the transcriptome of iM1 macrophages (reprogrammed M2-like macrophages).^2,3

Quantitative gene expression and cytokine secretion analyses indicate that in vitro repolarization of M2-like macrophages to the iM1 phenotype is efficiently but incompletely achieved by knocking down the expression of the predicted regulators E2f1, Myc, Pparγ, and Stat6. Combined expression knockdown of these regulators reprogrammed more genes in the M1-like direction than single expression knockdown, suggesting a cumulative effect of these transcription factors on the regulation of M2-like to M1-like polarization.

Scientific Resources

Learn More Macrophage Biology

Download M1 vs. M2 Macrophages

Learn More Akt Signaling in Macrophages

Learn More Isolation and Identification of Macrophages

Q & A

Q: What is the success rate of macrophage reprogramming using gene regulatory networks?

A: We have made significant progress in macrophage reprogramming with our gene regulatory network technology. By optimizing transcription factor combinations and regulatory logic, we have achieved industry-leading success rates. Specifically, we utilize the dynamic regulation of transcription and the development of a cell transplantation system that induces reprogramming to improve reprogramming efficiency.

Q: Is the function of reprogrammed macrophages stable?

A: We attach great importance to the functional stability of reprogrammed macrophages. Our tracking studies show that reprogrammed macrophages maintain good functional and phenotypic stability.

Q: What are the advantages of your technology over traditional methods?

A: Our technology offers several significant advantages.

• Efficiency: By optimizing gene regulatory networks and logic combinations, we have significantly improved reprogramming efficiency.
• Precision: Our method can precisely control the cell fate determination process and reduce non-specific differentiation.
• Customizability: We can tailor reprogramming strategies and cellular functions to the needs of different disease models.

Q: How do you ensure quality control during reprogramming?

A: Quality control is one of our main concerns. We utilize multiple levels of quality control measures.

• Comprehensive gene expression analysis
• Automatically categorized and counted
• Monitor the changes of cell status during the reprogramming process in real time

These measures ensure that we can provide high-quality, functionally stable reprogrammed macrophages.