Single cell and population transcriptomics reveal epithelial remodeling in type 2-high asthma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA605722 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11050949_1.fastq.gz | Fastqsanger.gz | |||
| SRR11050949_2.fastq.gz | Fastqsanger.gz | |||
| SRR11050950_1.fastq.gz | Fastqsanger.gz | |||
| SRR11050950_2.fastq.gz | Fastqsanger.gz | |||
| SRR11050951_1.fastq.gz | Fastqsanger.gz |
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Project description:The type 2 cytokine-high asthma endotype (T2H) is characterized by IL-13-driven mucus obstruction of the airways. To further investigate this incompletely understood pathobiology, we characterize IL-13 effects on human airway epithelial cell cultures using single-cell RNA sequencing, finding that IL-13 generates a distinctive transcriptional state for each cell type. Specifically, we discover a mucus secretory program induced by IL-13 in all cell types which converts both mucus and defense secretory cells into a metaplastic state with emergent mucin production and secretion, while leading to ER stress and cell death in ciliated cells. The IL-13-remodeled epithelium secretes a pathologic, mucin-imbalanced, and innate immunity-depleted proteome that arrests mucociliary motion. Signatures of IL-13-induced cellular remodeling are mirrored by transcriptional signatures characteristic of the nasal airway epithelium within T2H versus T2-low asthmatic children. Our results reveal the epithelium-wide scope of T2H asthma and present candidate therapeutic targets for restoring normal epithelial function.
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