Omics · study · 2026
A human organoid model of alveolar regeneration reveals distinct epithelial responses to interferon-gamma
Listed in NCBI GEO
Chronic obstructive pulmonary disease (COPD) is characterized by inflammation and emphysema, leading to progressive alveolar destruction.
Description
Currently, no therapies effectively regenerate the alveolar epithelium. Here, we developed and characterized a feeder- and serum-free primary adult human organoid model to investigate how inflammatory conditions influence alveolar regeneration.
Using Wnt activation and heregulin-β, we achieved long-term expansion of progenitor cells, while AT2 maturation protocols enhanced surfactant production, including the formation of tubular myelin. Introducing a LATS inhibitor to the expansion conditions induced an AT1 differentiation program without eliminating AT2 cells. Single-cell RNA-sequencing revealed multipotent progenitor-like populations, reflecting a state of heightened plasticity associated with regeneration.
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To model the effects of inflammation, we exposed these organoids to cytokines elevated in COPD. Notably, interferon-gamma (IFN-γ) exerted distinct effects on AT1 and AT2 cells: while it was cytotoxic to AT1 cells, it promoted growth in regenerating AT2 cells in a dose- and time-dependent manner. These findings underscore the nuanced influence of pro-inflammatory cytokines on alveolar regeneration.
Our organoid model provides a reductionist platform for mechanistic studies in human cells, aiming to identify therapies that prevent alveolar destruction and improve alveolar regeneration in COPD
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE287nnn/GSE287209 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287209 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1211630 ncbi.nlm.nih.gov/bioproject/PRJNA1211630 ↗
project · from NCBI GEO
- PubMed 41992061 pubmed.ncbi.nlm.nih.gov/41992061 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE287209 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |