Cyclic Stretch Promotes Cellular Reprogramming Process through Cytoskeletal-Nuclear Mechano-Coupling and Epigenetic...

Area of Science:

• Cell Biology
• Biophysics
• Regenerative Medicine

Background:

• Cellular reprogramming is crucial for regenerative therapy, disease modeling, and drug discovery.
• Biophysical cues influence cell fate, but the role of external physical forces in reprogramming is not fully understood.

Purpose of the Study:

• To investigate the impact of temporal cyclic-stretching on the efficiency of induced pluripotent stem cell (iPSC) production.
• To elucidate the underlying mechanotransduction and epigenetic mechanisms involved in stretch-enhanced reprogramming.

Main Methods:

• Fibroblasts were subjected to temporal cyclic-stretching.
• Induced pluripotent stem cell (iPSC) generation and characterization (pluripotency markers, in vivo functionality).
• Bulk and single-cell RNA-sequencing, genome-wide ChIP-sequencing, and pharmacological inhibition were employed to analyze molecular and epigenetic changes.

Main Results:

• Cyclic-stretching significantly enhanced iPSC production efficiency.
• Stretched iPSCs expressed pluripotency markers and showed in vivo functionality.
• Mechanisms involved increased cell division, mesenchymal-epithelial transition, activation of mechanosensitive molecules (integrins, YAP), and epigenetic modifications (H3K9 methylation downregulation).

Conclusions:

• Temporal cyclic-stretching is a potent physical stimulus that enhances cellular reprogramming via mechanotransduction and epigenetic alterations.
• This study establishes a link between physical forces, mechanotransduction, epigenetic changes, and gene expression in iPSC generation.
• Findings have significant implications for advancing cell biology, tissue engineering, and regenerative medicine.