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ETVs dictate hPSC differentiation by tuning biophysical properties

ABSTRACT: ETVs dictate hPSC differentiation by tuning biophysical properties

PROVIDER: PRJNA947085 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23927884_1.fastq.gz	Fastqsanger.gz
	SRR23927884_2.fastq.gz	Fastqsanger.gz
	SRR23927885_1.fastq.gz	Fastqsanger.gz
	SRR23927885_2.fastq.gz	Fastqsanger.gz
	SRR23927886_1.fastq.gz	Fastqsanger.gz

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ETVs dictate hPSC differentiation by tuning biophysical properties

Project description:Stem cells maintain a dynamic dialogue 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 enhanced 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 abolished pancreatic progenitor formation. Single-cell RNA sequencing and follow-up assays revealed 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.

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