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

A synthetic?biology?based strategy is employed to fabricate cell?reprogramming?inspired dynamically responsive hydrogel, and it faithfully senses metabolic remodeling and extracellular acidification during cell reprogramming, responding by changing its mechanical properties accordingly. The cell?reprogramming?inspired dynamically responsive hydrogel boosts the generation of induced pluripotent stem cells from mouse and human somatic cells via phase?separated yes?associated protein (YAP) 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 are time?consuming and inefficient. Here, a cell?reprogramming?inspired dynamically responsive hydrogel is fabricated via a synthetic?biology?based strategy. Human and mouse somatic cells (including senescent cells) are efficiently reprogrammed into iPSCs that exhibit key features of embryonic stem cells. The cell?reprogramming?responsive hydrogel possesses dynamic bioresponsiveness, and it faithfully senses metabolic remodeling and extracellular acidification during cell reprogramming, responding by changing its mechanical properties accordingly. Mechanistic study demonstrates that the autonomous change of the mechanical properties of the 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, this study reveals the robust induction of pluripotency by coordination of cell?reprogramming?inspired dynamically responsive hydrogel and phase?separated biomolecular condensates.

Publication date: 14/05/2023

Advanced Materials

      

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 870292.