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Published on: June 17, 2016
Single-Cell RNA Sequencing Reveals the Interaction of Injected ADSCs with Lung-Originated Cells in Mouse Pulmonary
Mamatali Rahman1,2, Zhao-Yan Wang1,2, Jun-Xiang Li1,2,3,4
1MOE Key Laboratory of Bioinformatics, Center for Synthetic and System Biology, Tsinghua University, Beijing 100084, China.
Abstract:
Pulmonary fibrosis (PF) is a severe chronic lung disease with little effective treatment options other than lung transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have been shown to exert therapeutic effects on PF, but the underlying mechanisms remain to be further elucidated. Here, we show the interaction of ADSCs and lung-originated cells at the single-cell level, using bleomycin- (BLM-) induced mice PF model and green fluorescent protein- (GFP-) labeled mouse ADSCs. The intratracheally injected ADSCs were successfully recollected with flow cytometry and, together with lung-originated cells, were subjected to single-cell RNA sequencing (scRNA-seq). The ADSC treatment drastically changed the transcriptomic profile and composition of lung cells, especially macrophages. We explored the signal pathway interactions between ADSCs and lung-originated cells, showing potentially regulative pathways including NGR, ANNEXIN, HGF, and PERIOSTIN. Our data indicate that the injected ADSCs increased the number of Trem2 + antiinflammatory lung macrophages and lowered further inflammation and fibrosis in the lung. Our work realized the direct analysis of injected ADSCs to explore its in vivo interaction with the lung environment under PF and may provide critical information for future engineering of ADSCs to achieve better therapeutic effects in PF.
Insights
Adipose-derived mesenchymal stem cells (ADSCs) reduce lung fibrosis by modulating macrophage populations. This study reveals how ADSCs interact with lung cells to decrease inflammation and fibrosis in pulmonary fibrosis models.
Area of Science:
- Regenerative Medicine
- Immunology
- Cell Biology
Background:
- Pulmonary fibrosis (PF) is a debilitating lung disease with limited treatment options.
- Adipose-derived mesenchymal stem cells (ADSCs) show therapeutic potential for PF, but mechanisms are unclear.
Purpose of the Study:
- To elucidate the in vivo interaction mechanisms of ADSCs with the lung microenvironment in a mouse model of PF.
- To identify specific cellular and molecular pathways modulated by ADSCs during PF treatment.
Main Methods:
- Utilized a bleomycin-induced mouse model of pulmonary fibrosis.
- Employed green fluorescent protein-labeled ADSCs and single-cell RNA sequencing (scRNA-seq) for detailed analysis.
- Analyzed transcriptomic profiles and cell composition changes in lung tissues.
Main Results:
- ADSC treatment altered lung cell transcriptomes, particularly affecting macrophage populations.
- Identified potential regulatory pathways including NGR, ANNEXIN, HGF, and PERIOSTIN.
- Observed an increase in Trem2+ anti-inflammatory macrophages, correlating with reduced lung inflammation and fibrosis.
Conclusions:
- ADSCs modulate lung immunity and reduce fibrosis by promoting anti-inflammatory macrophage phenotypes.
- Provides critical insights into ADSC-lung cell interactions for optimizing cell-based therapies for PF.
- Highlights the potential of targeting macrophage polarization for PF treatment.
