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| Status |
Public on Jul 13, 2020 |
| Title |
Single cell and population transcriptomics reveal epithelial remodeling in type 2-high asthma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
BACKGROUND: The type 2 cytokine-high asthma endotype (T2H) is characterized by IL-13-driven mucus obstruction of the airways. To investigate this poorly understood pathobiology, we characterized IL-13 effects on human airway epithelial cultures using single cell RNA-sequencing, finding that IL-13 generated a novel transcriptional state for each cell type. Specifically, we discovered a mucus secretory program induced by IL-13 in all cell types which converted 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 secreted a pathologic, mucin-imbalanced, and innate immunity-depleted proteome that arrested mucociliary motion. Signatures of IL-13-induced cellular remodeling were 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 novel therapeutic targets for restoring normal epithelial function.
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| Overall design |
Single cell transcriptomics was carried out for experiments involving either acute (48 hours) or chronic (11 days) stimulation with IL-13 (or mock stimulation with BSA) of air-liquid interface (ALI) cultures grown from epithelial cells taken from two tracheal donors. For the acute stimulation experiment, we sequenced a total of 2,385 cells, plus positive and negative controls (1,894 remaining after QC). For the chronic stimulation experiment, we sequenced a total of 802 single cells (756 remaining after QC and batch correction).
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| Contributor(s) |
Jackson ND, Everman JL, Chioccioli M, Goldfarbmuren KC, Sajuthi SP, Rios C, Powell R, Armstrong M, Gomez J, Michel C, Eng C, Oh SS, Rodriguez-Santana J, Feriani L, Cicuta P, Reisdorph N, Burchard EG, Seibold MA |
| Citation(s) |
32640237 |
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| Submission date |
Feb 10, 2020 |
| Last update date |
Jul 13, 2020 |
| Contact name |
Nathan Jackson |
| E-mail(s) |
[email protected]
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| Organization name |
National Jewish Health
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| Department |
Center for Genes, Environment, and Health
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| Street address |
1400 Jackson St.
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| City |
Denver |
| State/province |
CO |
| ZIP/Postal code |
80206 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (3) |
| GSM4304270 |
ScRNA-seq of airway epithelial tracheal cultures with acute IL-13 stimulation [Acute_stim_91497] |
| GSM4304271 |
ScRNA-seq of airway epithelial tracheal cultures with acute IL-13 stimulation [Acute_stim_94576] |
| GSM4304272 |
ScRNA-seq of airway epithelial tracheal cultures with chronic IL-13 stimulation [Chronic_stim_97570] |
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| Relations |
| BioProject |
PRJNA605722 |
| SRA |
SRP247905 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE145013_IL13_acute_metadata.txt.gz |
7.0 Kb |
(ftp)(http) |
TXT |
| GSE145013_IL13_acute_norm_matrix.txt.gz |
48.0 Mb |
(ftp)(http) |
TXT |
| GSE145013_IL13_acute_raw_matrix.txt.gz |
7.4 Mb |
(ftp)(http) |
TXT |
| GSE145013_IL13_acute_seurat.rda.gz |
417.6 Mb |
(ftp)(http) |
RDA |
| GSE145013_RAW.tar |
242.0 Mb |
(http)(custom) |
TAR (of RDA, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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