ETVs dictate hPSC differentiation by tuning biophysical properties.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40011454.
- Also identified by DOI 10.1038/s41467-025-56591-6 and PMC identifier 11865489.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Stem cells maintain a dynamic dialog with their niche, integrating biochemical and biophysical cues to modulate cellular behavior. Yet, the transcriptional networks that regulate cellular biophysical properties remain poorly defined. Here, we leverage human pluripotent stem cells (hPSCs) and two morphogenesis models - gastruloids and pancreatic differentiation - to establish ETV transcription factors as critical regulators of biophysical parameters and lineage commitment. Genetic ablation of ETV1 or ETV1/ETV4/ETV5 in hPSCs enhances cell-cell and cell-ECM adhesion, leading to aberrant multilineage differentiation including disrupted germ-layer organization, ectoderm loss, and extraembryonic cell overgrowth in gastruloids. Furthermore, ETV1 loss abolishes pancreatic progenitor formation. Single-cell RNA sequencing and follow-up assays reveal dysregulated mechanotransduction via the PI3K/AKT signaling. Our findings highlight the importance of transcriptional control over cell biophysical properties and suggest that manipulating these properties may improve in vitro cell and tissue engineering strategies.
Medical subject headings
- Cell Differentiation
- Transcription Factors
- Pluripotent Stem Cells
- DNA-Binding Proteins