Related Experiment Video
Updated: Jun 15, 2026
Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Systems level identification of a matrisome-associated macrophage polarisation state in multi-organ fibrosis
John F Ouyang1,2, Kunal Mishra1,2, Yi Xie1,2
1Centre for Computational Biology, Duke-NUS Medical School, Singapore, Singapore.
Abstract:
Tissue fibrosis affects multiple organs and involves a master-regulatory role of macrophages which respond to an initial inflammatory insult common in all forms of fibrosis. The recently unravelled multi-organ heterogeneity of macrophages in healthy and fibrotic human disease suggests that macrophages expressing osteopontin (SPP1) associate with lung and liver fibrosis. However, the conservation of this SPP1+ macrophage population across different tissues and its specificity to fibrotic diseases with different etiologies remain unclear. Integrating 15 single-cell RNA-sequencing datasets to profile 235,930 tissue macrophages from healthy and fibrotic heart, lung, liver, kidney, skin, and endometrium, we extended the association of SPP1+ macrophages with fibrosis to all these tissues. We also identified a subpopulation expressing matrisome-associated genes (e.g., matrix metalloproteinases and their tissue inhibitors), functionally enriched for ECM remodelling and cell metabolism, representative of a matrisome-associated macrophage (MAM) polarisation state within SPP1+ macrophages. Importantly, the MAM polarisation state follows a differentiation trajectory from SPP1+ macrophages and is associated with a core set of regulon activity. SPP1+ macrophages without the MAM polarisation state (SPP1+MAM-) show a positive association with ageing lung in mice and humans. These results suggest an advanced and conserved polarisation state of SPP1+ macrophages in fibrotic tissues resulting from prolonged inflammatory cues within each tissue microenvironment.
Insights
Osteopontin-positive (SPP1+) macrophages are linked to fibrosis across multiple organs. A specialized subpopulation, matrisome-associated macrophages (MAMs), drives extracellular matrix remodeling in fibrotic diseases.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Tissue fibrosis is a significant health concern affecting multiple organs.
- Macrophages play a crucial role in the inflammatory response underlying fibrosis.
- Previous studies identified osteopontin-expressing (SPP1+) macrophages in lung and liver fibrosis, but their role in other tissues and fibrotic etiologies was unclear.
Purpose of the Study:
- To investigate the conservation and specificity of SPP1+ macrophages in various fibrotic human tissues.
- To identify and characterize macrophage subpopulations associated with fibrosis across different organs.
- To explore the functional role and differentiation trajectory of these macrophage populations in fibrotic disease.
Main Methods:
- Integrated 15 single-cell RNA-sequencing datasets from healthy and fibrotic human heart, lung, liver, kidney, skin, and endometrium.
- Analyzed 235,930 tissue macrophages to identify distinct populations and their gene expression profiles.
- Investigated the association of SPP1+ macrophages and their subpopulations with fibrosis and aging.
Main Results:
- SPP1+ macrophages are associated with fibrosis in all examined tissues (heart, lung, liver, kidney, skin, endometrium).
- A subpopulation, termed matrisome-associated macrophages (MAMs), was identified within SPP1+ macrophages, characterized by ECM-remodeling and metabolic genes.
- MAMs exhibit a differentiation trajectory from SPP1+ macrophages and are linked to core regulon activity, while SPP1+MAM- macrophages associate with aging.
Conclusions:
- SPP1+ macrophages represent a conserved cellular component across diverse fibrotic tissues.
- The development of MAMs signifies an advanced polarization state within SPP1+ macrophages, crucial for ECM remodeling in fibrosis.
- These findings suggest prolonged inflammatory cues drive conserved macrophage polarization states in fibrotic microenvironments.
