Omics · study · 2026
The chromatin remodeling complex PRC2 safeguards cell fate in alveolar epithelial type 2 cells
Listed in NCBI GEO
Maintenance of the gas exchange surface throughout life and regeneration of the lung after injury requires tight regulation of epithelial cell fate and function.
Description
Alveolar epithelial type 2 (AT2) cells serve as the progenitors of the distal epithelium, differentiating into alveolar epithelial type 1 (AT1) cells or proliferating to maintain the quorum of AT2 cells. Here we describe the role of the chromatin regulator polycomb repressive complex 2 (PRC2) in the maintenance of AT2 cell fate in the adult alveolus.
Cross-species single-cell transcriptomic analyses identified PRC2 activation in proliferative AT2 populations. PRC2 loss of function in human iPSC-derived AT2 (iAT2) cells and primary murine AT2 cells in vitro resulted in loss of AT2 cell state and emergence of programs reminiscent of alveolar-basal intermediate (ABI) cell states, while overexpression of the PRC2 enzymatic component EZH2 in human iAT2 cells augmented the AT2 cell program.
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Genetic loss of PRC2 function in the AT2 lineage in adult mice in vivo led to emphysematous remodeling of the lung and induced a time-dependent series of transitions of AT2 cells through an ABI state into Krt5+ basal-like cells. Comparison of murine ABI cells to human ABI cells demonstrates de-repression of canonical PRC2 targets during transition to ABI and basal-like states in humans, implicating PRC2 as a conserved regulator of AT2 cell fate.
Together, these findings define PRC2 complex function during AT2 cell self-renewal as a critical guardrail for maintaining epithelial cell fate in the adult lung.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325698 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325698 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1441478 ncbi.nlm.nih.gov/bioproject/PRJNA1441478 ↗
project · from NCBI GEO
- PubMed 41867819 pubmed.ncbi.nlm.nih.gov/41867819 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE325698 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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:10090 | 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 |