Omics · study · 2026
Endothelial KRASG12V signaling drives aberrant morphogenesis and establishes an AVM transcriptional identity in primary human endothelial cells
Listed in NCBI GEO
Somatic activating mutations in KRAS are found in the endothelium of the majority of sporadic brain arteriovenous malformations (bAVMs), yet the consequences of oncogenic KRAS signaling in endothelial cells during active vessel morphogenesis remain incompletely characterized.
Description
We expressed KRASG12V in primary human umbilical vein endothelial cells using a doxycycline-inducible lentiviral system and examined morphogenic behavior, proliferation, migration, and transcriptional output in a three-dimensional planar co-culture angiogenesis assay.
KRASG12V-expressing cells failed to organize into vessel-like networks, instead forming compact sheet-like structures that persisted through day 12. A transient proliferative phase at days 3–5 resolved to control levels by day 12, consistent with preserved sensitivity to contact inhibition rather than unrestricted growth. Enhanced migration at day 5 was accompanied by upregulation of a focal adhesion and matrix remodeling program centered on ITGB3, PLAU, PLAUR, and PIK3CG.
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Translating ribosome-affinity purification sequencing (TRAP-seq) of the EC-specific translatome across four independent donor pools revealed progressive acquisition of an AVM-associated transcriptional identity by day 12, including upregulation of ACVRL1, ENG, JAG1, NOTCH1, ANGPT2, and TEK, with concordance to human bAVM nidus endothelium at both the gene and pathway level. Pharmacological inhibition with Alpelisib (PI3Kα), Trametinib (MEK), and Pazopanib (VEGFR2) demonstrated that PI3K is the principal organizer of the morphogenic phenotype.
These findings characterize a KRASG12V-driven program in endothelial cells that recapitulates core transcriptional features of bAVM endothelium in a primary cell model.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336689 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336689 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1482393 ncbi.nlm.nih.gov/bioproject/PRJNA1482393 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Sequencing 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE336689 | 14 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[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |