Single-cell RNA-sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis

Dataset overview

Participants 30

Samples 34

Reuse readiness 6.1/10 evidence-backed score

Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis.

Habermann AC, Gutierrez AJ, Bui LT, Yahn SL, Winters NI, Calvi CL, Peter L, Chung MI, et al. · Science advances · 2020

Abstract

Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5- /KRT17 + pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis.

doi:10.1126/sciadv.aba1972 ↗ PMID 32832598 ↗ PMC7439444 ↗

Study facts

Organism: Homo sapiens
Platform: 10X 5' Gene Expression (GEX) Library Construction
Age group: —
Disease groups: —
Anatomical sites: lung

Data availability

Raw counts
Processed matrix

File types CSVMTXRDSTSVTXT

Lung Biopsy34

Accession	Sample	Tissue	Molecule
`GSM4037297`	Lung Biopsy, PF, VUILD48	Lung Biopsy	total RNA
`GSM4037298`	Lung Biopsy, PF, VUILD54	Lung Biopsy	total RNA
`GSM4037299`	Lung Biopsy, PF, VUILD53	Lung Biopsy	total RNA
`GSM4037300`	Lung Biopsy, PF, VUILD55	Lung Biopsy	total RNA
`GSM4037301`	Lung Biopsy, control, VUHD65	Lung Biopsy	total RNA
`GSM4037302`	Lung Biopsy, control, VUHD66	Lung Biopsy	total RNA
`GSM4037303`	Lung Biopsy, PF, VUILD57	Lung Biopsy	total RNA
`GSM4037304`	Lung Biopsy, PF, VUILD58	Lung Biopsy	total RNA
`GSM4037305`	Lung Biopsy, control, VUHD67	Lung Biopsy	total RNA
`GSM4037306`	Lung Biopsy, control, VUHD68	Lung Biopsy	total RNA
`GSM4037307`	Lung Biopsy, PF, VUILD59-2	Lung Biopsy	total RNA
`GSM4037308`	Lung Biopsy, PF, VUILD59-1	Lung Biopsy	total RNA
`GSM4037309`	Lung Biopsy, control, VUHD69	Lung Biopsy	total RNA
`GSM4037310`	Lung Biopsy, PF, VUILD60-2	Lung Biopsy	total RNA
`GSM4037311`	Lung Biopsy, PF, VUILD60-1	Lung Biopsy	total RNA
`GSM4037312`	Lung Biopsy, PF, TILD001	Lung Biopsy	total RNA
`GSM4037313`	Lung Biopsy, control, THD0001	Lung Biopsy	total RNA
`GSM4037314`	Lung Biopsy, PF, VUILD61-2	Lung Biopsy	total RNA
`GSM4037315`	Lung Biopsy, PF, VUILD61-1	Lung Biopsy	total RNA
`GSM4037316`	Lung Biopsy, control, VUHD70	Lung Biopsy	total RNA
`GSM4037317`	Lung Biopsy, PF, VUILD62-1	Lung Biopsy	total RNA
`GSM4037318`	Lung Biopsy, PF, VUILD62-2	Lung Biopsy	total RNA
`GSM4037319`	Lung Biopsy, PF, TILD015	Lung Biopsy	total RNA
`GSM4037320`	Lung Biopsy, PF, VUILD63	Lung Biopsy	total RNA
`GSM4037321`	Lung Biopsy, PF, VUILD64	Lung Biopsy	total RNA
`GSM4037322`	Lung Biopsy, PF, VUILD65	Lung Biopsy	total RNA
`GSM4037323`	Lung Biopsy, control, VUHD71	Lung Biopsy	total RNA
`GSM4037324`	Lung Biopsy, control, THD0002	Lung Biopsy	total RNA
`GSM4037325`	Lung Biopsy, control, THD0005	Lung Biopsy	total RNA
`GSM4037326`	Lung Biopsy, PF, TILD006	Lung Biopsy	total RNA
`GSM4037327`	Lung Biopsy, PF, TILD010	Lung Biopsy	total RNA
`GSM4037328`	Lung Biopsy, PF, TILD030	Lung Biopsy	total RNA
`GSM4037329`	Lung Biopsy, PF, TILD028	Lung Biopsy	total RNA
`GSM4037330`	Lung Biopsy, PF, TILD019	Lung Biopsy	total RNA

Strengths & limitations for reuse

Strengths

Raw counts are advertised
Processed matrices are advertised
Cell metadata are advertised
Participant counts are documented

Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

Field	Value	Evidence
`assay.assay_type`	single-cell RNA sequencing	Expression profiling by high throughput sequencing Section `series_type`, offset —
`assay.library_chemistry`	10X 5' Gene Expression (GEX)	10X 5' Gene Expression (GEX) Library Construction Section `samples.extract_protocol`, offset —
`assay.platform`	10X 5' Gene Expression (GEX) Library Construction	10X 5' Gene Expression (GEX) Library Construction Section `samples.extract_protocol`, offset —
`assay.reference_genome`	hg38	Genome_build: hg38 Section `samples.data_processing`, offset —
`assay.sequencing_type`	scrna_seq	We performed single-cell RNA-sequencing (scRNA-seq) of single-cell suspensions generated from non-fibrotic control and pulmonary fibrosis (PF) lungs Section `series_overall_design`, offset —

Cohort

Field Value Evidence

Field	Value	Evidence
`cohort.non_ibd_controls`	10	Analysis of over 114,000 cells from 20 PF and 10 control lungs identified 31 distinct cell types. Section `series_summary`, offset —
`cohort.total_participants`	30	Analysis of over 114,000 cells from 20 PF and 10 control lungs identified 31 distinct cell types. Section `series_summary`, offset —

cohort.non_ibd_controls

10

Analysis of over 114,000 cells from 20 PF and 10 control lungs identified 31 distinct cell types.

Section series_summary, offset —

cohort.total_participants

30