Omics · study · 2026
Gas6 promotes Cardiomyocyte Proliferation and Heart Regeneration
Listed in NCBI GEO
Ischemic heart disease remains a leading cause of mortality, with limited adult cardiac regeneration due to insufficient cardiomyocyte proliferation.
Description
This study investigates the role of Growth Arrest-Specific Gene 6 (Gas6) in regulating cardiomyocyte cell cycle and promoting cardiac repair. Gas6 expression declines postnatally in cardiomyocytes but increases during neonatal heart regeneration following myocardial infarction (MI).
Cardiomyocyte-specific Gas6 knockout (Gas6CKO) mice exhibited reduced cardiomyocyte proliferation, decreased total cardiomyocyte numbers, and delayed-onset heart failure with ventricular dilation by ~250 days, as confirmed by transcriptomic analysis revealing downregulation of cell cycle pathways and upregulation of fibrotic and contractile genes in Gas6CKO versus control hearts at 250 days. Conversely, AAV9-mediated cardiomyocyte-specific Gas6 overexpression enhanced neonatal cardiomyocyte proliferation, dedifferentiation, and hyperplastic growth, while in adult MI models, it improved cardiac function, reduced infarct size, and increased proliferative markers (Ki67, pH3, Aurora B) in the border zone.
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Bulk RNA-sequencing of primary mouse cardiomyocytes overexpressing Ad-Gas6 versus controls identified upregulated cell cycle and mitotic pathways, alongside downregulated cardiac contraction and extracellular matrix organization, with transcription factor enrichment highlighting Yap-mediated activation via TEAD2 and E2F1. Mechanistically, Gas6 binds Sav1 to disrupt the Sav1-Mst1 complex, inhibiting Hippo pathway phosphorylation, promoting Yap nuclear translocation, and driving cell cycle gene expression.
These findings position Gas6 as a therapeutic target for cardiac regeneration in ischemic heart disease.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306068 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306068 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1309049 ncbi.nlm.nih.gov/bioproject/PRJNA1309049 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cardiovascular disease 65% · Disease 75% · Heart 75% · Myocardial infarction 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE306068 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:cardiovascular-disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[disease].local:disease:myocardial-infarction | 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: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 |