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| Status |
Public on Nov 01, 2022 |
| Title |
Single-cell transcriptomic characterization reveals the landscape of airway remodeling and inflammation in a cynomolgus monkey model of asthma |
| Organism |
Macaca fascicularis |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Monkey disease models, which are comparable to humans in terms of genetic, anatomical, and physiological characteristics, are important for understanding disease mechanisms and evaluating the efficiency of biological treatments. Here, we established an A.suum-induced model of asthma in cynomolgus monkeys to profile airway inflammation and remodeling in the lungs by single-cell transcriptomic sequencing (scRNA-seq). The asthma model results in airway hyperresponsiveness and remodeling, demonstrated by pulmonary function test and histological characterization. scRNA-seq reveals that the model elevates the numbers of stromal, epithelial and mesenchymal cells (MCs). Particularly, the model increases the numbers of endothelial cells (ECs), fibroblasts (Fibs) and smooth muscle cells (SMCs) in the lungs, with upregulated gene expression associated with cell functions enriched in cell migration and angiogenesis in ECs and Fibs, and VEGF-driven cell proliferation, apoptotic process and complement activation in SMCs. Interestingly, we discover a novel Fib subtype that mediates type I inflammation in the asthmatic lungs. Moreover, MCs cells in the asthmatic lungs are found to regulate airway remodeling and immunological responses, with elevated gene expression enriched in cell migration, proliferation, angiogenesis and innate immunological responses. Despite the fact that the numbers of epithelial cells in the asthma lungs do not change at the time of lung tissue collection, their gene expressions are significantly altered, with an enrichment in the biological processes of IL-17 signaling pathway and apoptosis in the majority of subtypes of epithelial cells. Moreover, the ubiquitin process and DNA repair are more prevalent in ciliated epithelial cells. Last, cell-to-cell interaction analysis reveals a complex network among stromal cells, MCs and macrophages that contribute to the development of asthma and airway remodeling. Our findings provide a critical resource for understanding the principle underlying airway remodeling and inflammation in a monkey model of asthma, as well as valuable hints for the future treatment of asthma, especially the airway remodeling-characterized refractory asthma.
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| Overall design |
Lung tissues were obtained from the control and asthma groups.The tissues were dissociated into single cells in dissociation solution.Single cell suspensions were loaded to 10× Chromium (10× Genomics, USA) to capture more than 3,000 single cells for the Single-cell 3′ Library using Gel Bead Kit V3 (1000075, 10× Genomics, USA) according to the manufacturer’s instructions. The following cDNA amplification and library construction steps were performed according to the manufacturer’s recommendation. Sequencing was performed on the NovaSeq6000 sequencer (Illumina, USA) with a minimum depth of 60,000~90,000 reads per cell and 150 bp (PE150) paired-end reads performed by LC-Bio Technology Co., Ltd (China).
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| Contributor(s) |
Xie Y, Li S, Shen H, Wang Y, Dong X, Pan C, Zhu C, Qi H, Wang Y, Wei H, Xie Q, Wu L |
| Citation(s) |
36439114 |
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| Submission date |
Sep 10, 2022 |
| Last update date |
Dec 09, 2022 |
| Contact name |
Yicheng Xie |
| E-mail(s) |
[email protected]
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| Phone |
18367153988
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| Organization name |
Children’s Hospital Zhejiang University School of Medicine
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| Street address |
3333 Binsheng Rd
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| City |
Hangzhou |
| ZIP/Postal code |
310052 |
| Country |
China |
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| Platforms (1) |
| GPL28212 |
Illumina NovaSeq 6000 (Macaca fascicularis) |
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| Samples (6)
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| GSM6571329 |
scRNA-Seq of lung: adult male cynomolgus monkey C1 |
| GSM6571330 |
scRNA-Seq of lung: adult male cynomolgus monkey C2 |
| GSM6571331 |
scRNA-Seq of lung: adult male cynomolgus monkey C3 |
| GSM6571332 |
scRNA-Seq of lung: adult male cynomolgus monkey M8 |
| GSM6571333 |
scRNA-Seq of lung: adult male cynomolgus monkey M10 |
| GSM6571334 |
scRNA-Seq of lung: adult male cynomolgus monkey M11 |
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| Relations |
| BioProject |
PRJNA879072 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213085_RAW.tar |
168.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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