Related Experiment Video
Updated: Oct 28, 2025
Analyzing Ex Vivo Metabolic Flux in Splenic and Cardiac Macrophages and Bone Marrow Monocytes
Published on: March 28, 2025
Single-cell analysis identifies distinct macrophage phenotypes associated with prodisease and proresolving functions
Yasmin Henlon1,2, Kavita Panir1,2, Iona McIntyre1,2
1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
Abstract:
Endometriosis negatively impacts the health-related quality of life of 190 million women worldwide. Novel advances in nonhormonal treatments for this debilitating condition are desperately needed. Macrophages play a vital role in the pathophysiology of endometriosis and represent a promising therapeutic target. In the current study, we revealed the full transcriptomic complexity of endometriosis-associated macrophage subpopulations using single-cell analyses in a preclinical mouse model of experimental endometriosis. We have identified two key lesion-resident populations that resemble i) tumor-associated macrophages (characterized by expression of Folr2, Mrc1, Gas6, and Ccl8+) that promoted expression of Col1a1 and Tgfb1 in human endometrial stromal cells and increased angiogenic meshes in human umbilical vein endothelial cells, and ii) scar-associated macrophages (Mmp12, Cd9, Spp1, Trem2+) that exhibited a phenotype associated with fibrosis and matrix remodeling. We also described a population of proresolving large peritoneal macrophages that align with a lipid-associated macrophage phenotype (Apoe, Saa3, Pid1) concomitant with altered lipid metabolism and cholesterol efflux. Gain of function experiments using an Apoe mimetic resulted in decreased lesion size and fibrosis, and modification of peritoneal macrophage populations in the preclinical model. Using cross-species analysis of mouse and human single-cell datasets, we determined the concordance of peritoneal and lesion-resident macrophage subpopulations, identifying key similarities and differences in transcriptomic phenotypes. Ultimately, we envisage that these findings will inform the design and use of specific macrophage-targeted therapies and open broad avenues for the treatment of endometriosis.
Insights
Researchers identified distinct macrophage populations in endometriosis, revealing potential therapeutic targets. Targeting lipid metabolism with an Apoe mimetic reduced lesion size and fibrosis in a preclinical model, offering new nonhormonal treatment avenues.
Area of Science:
- Immunology and Molecular Biology
- Reproductive Medicine
Background:
- Endometriosis affects 190 million women globally, significantly impairing quality of life.
- Current nonhormonal treatment options for endometriosis are limited, highlighting the need for novel therapeutic strategies.
- Macrophages are key players in endometriosis pathophysiology, presenting a promising target for intervention.
Purpose of the Study:
- To elucidate the transcriptomic landscape of macrophage subpopulations within endometriosis lesions and peritoneal fluid.
- To identify specific macrophage phenotypes associated with endometriosis progression and fibrosis.
- To explore the therapeutic potential of targeting macrophage populations, particularly those involved in lipid metabolism.
Main Methods:
- Single-cell RNA sequencing was employed to analyze macrophage subpopulations in a preclinical mouse model of experimental endometriosis.
- Cross-species analysis compared transcriptomic data from mouse and human endometriosis datasets.
- Gain-of-function experiments utilized an Apoe mimetic to assess therapeutic effects on lesion size, fibrosis, and macrophage populations.
Main Results:
- Two distinct lesion-resident macrophage populations were identified: tumor-associated macrophage-like cells promoting stromal cell activation and angiogenesis, and scar-associated macrophages linked to fibrosis and matrix remodeling.
- A proresolving peritoneal macrophage population with a lipid-associated phenotype and altered lipid metabolism was characterized.
- Treatment with an Apoe mimetic decreased endometriosis lesion size and fibrosis, alongside modulating peritoneal macrophage populations.
Conclusions:
- Single-cell transcriptomics reveals diverse macrophage subpopulations in endometriosis with distinct functional roles.
- Targeting lipid metabolism via Apoe mimetics shows promise as a nonhormonal therapeutic strategy for endometriosis.
- These findings provide a foundation for developing targeted macrophage-based therapies to treat endometriosis.
More Related Videos
06:22Isolation of Viable Adipocytes and Stromal Vascular Fraction from Human Visceral Adipose Tissue Suitable for RNA Analysis and Macrophage Phenotyping
Published on: October 27, 2020
07:46Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
