Cell Reprogramming-Inspired Dynamically Responsive Hydrogel Boosts the Induction of Pluripotency via Phase-Separated Biomolecular Condensates.

Induced pluripotent stem cells (iPSCs) have wide applications in disease modeling, personalized medicine and tissue engineering. The generation of iPSCs from somatic cells via transcriptional factor- or chemical molecule-based approaches is time-consuming and inefficient. Here, cell reprogramming-inspired dynamically responsive hydrogel is fabricated via a synthetic biology-based strategy. Human and mouse somatic cells (including senescent cells) have been efficiently reprogrammed into iPSCs that exhibit key features of embryonic stem cells. Cell reprogramming-responsive hydrogel possesses dynamic bioresponsiveness, which faithfully senses metabolic remodeling and extracellular acidification during cell reprogramming and responds by changing its mechanical properties accordingly. Mechanistic study demonstrate that the autonomous change of mechanical properties of cell reprogramming-responsive hydrogel elicits the formation of Yes-associated protein (YAP) biomolecular condensates with the appropriate timing during cell reprogramming, ensuring a faster and more efficient generation of iPSCs than conventional cell reprogramming approach. Taken together, our study reveals the robust induction of pluripotency by coordination of cell reprogramming-inspired dynamically responsive hydrogel and phase-separated biomolecular condensates. This article is protected by copyright. All rights reserved.