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| Status |
Public on Apr 06, 2020 |
| Title |
Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cigarette smoke first interacts with the lung through the cellularly diverse airway epithelium and goes on to drive development of most chronic lung diseases. Here, through single cell RNA-sequencing analysis of the tracheal epithelium from smokers and nonsmokers, we generate a comprehensive atlas of epithelial cell types and states, connect these into lineages, and define cell-specific responses to smoking. Our analysis infers multi-state lineages that develop into surface mucus secretory and ciliated cells and then contrasts these to the unique specification of submucosal gland (SMG) cells. Accompanying knockout studies reveal that tuft-like cells are the likely progenitor of both pulmonary neuroendocrine cells and CFTR-rich ionocytes. Our smoking analysis finds that all cell types, including protected stem and SMG populations, are affected by smoking through both pan-epithelial smoking response networks and hundreds of cell-specific response genes, redefining the penetrance and cellular specificity of smoking effects on the human airway epithelium.
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| Overall design |
For the in vivo dataset, we sequenced a total of 68,370 (36,248 after QC) epithelial cells from across 15 human tracheal donors (6 heavy smokers, 6 never-smokers, 2 light smokers, and 1 pediatric subject). For the in vitro dataset we sequenced a total of 8,722 (5,976 after QC) epithelial cells sampled from 20 time points along the differentiation process taken by air-liquid interface (ALI) cultures seeded from primary basal cells of 3 human tracheal donors (from ALI seed day to day 32 post-airlift)
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| Contributor(s) |
Goldfarbmuren KC, Jackson ND, Sajuthi SP, Dyjack N, Li KS, Rios CL, Plender EG, Montgomery MT, Everman JL, Bratcher PE, Vladar EK, Seibold MA |
| Citation(s) |
32427931 |
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| Submission date |
Jul 11, 2019 |
| Last update date |
Jun 01, 2020 |
| Contact name |
Nathan Jackson |
| E-mail(s) |
jacksonNa@njhealth.org
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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 (28)
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| Relations |
| BioProject |
PRJNA554141 |
| SRA |
SRP214324 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE134174_Processed_invitro_metadata.txt.gz |
47.9 Kb |
(ftp)(http) |
TXT |
| GSE134174_Processed_invitro_norm.txt.gz |
95.4 Mb |
(ftp)(http) |
TXT |
| GSE134174_Processed_invitro_raw.txt.gz |
14.3 Mb |
(ftp)(http) |
TXT |
| GSE134174_Processed_invivo_integrated.txt.gz |
779.8 Mb |
(ftp)(http) |
TXT |
| GSE134174_Processed_invivo_metadata.txt.gz |
244.1 Kb |
(ftp)(http) |
TXT |
| GSE134174_Processed_invivo_norm.txt.gz |
174.9 Mb |
(ftp)(http) |
TXT |
| GSE134174_Processed_invivo_raw.txt.gz |
139.0 Mb |
(ftp)(http) |
TXT |
| GSE134174_Processed_invivo_seurat.Rdata.gz |
2.8 Gb |
(ftp)(http) |
RDATA |
| GSE134174_T84_invitro_metadata.txt.gz |
18.6 Kb |
(ftp)(http) |
TXT |
| GSE134174_T85_invitro_metadata.txt.gz |
20.6 Kb |
(ftp)(http) |
TXT |
| GSE134174_T89_invitro_metadata.txt.gz |
20.5 Kb |
(ftp)(http) |
TXT |
| GSE134174_invitro_expression_matrix.txt.tar.gz |
16.4 Mb |
(ftp)(http) |
TAR |
| GSE134174_invivo_expression_matrix.txt.tar.gz |
227.1 Mb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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