TY - JOUR
T1 - Cell-Reprogramming-Inspired Dynamically Responsive Hydrogel Boosts the Induction of Pluripotency via Phase-Separated Biomolecular Condensates
AU - Zhu, Fei
AU - Yan, Na
AU - Lu, Xukun
AU - Xu, Junchao
AU - Gu, Haiyan
AU - Liang, Jie
AU - Cheng, Keman
AU - Wang, Xiaona
AU - Ma, Xiaotu
AU - Ma, Nana
AU - Zhao, Xiao
AU - Chen, Chunying
AU - Nie, Guangjun
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - cell-reprogramming-responsive hydrogels
KW - dynamic responsiveness
KW - induced pluripotent stem cells
KW - induction of pluripotency
KW - phase-separated biomolecular condensates
UR - http://www.scopus.com/inward/record.url?scp=85159091091&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159091091&partnerID=8YFLogxK
U2 - 10.1002/adma.202211609
DO - 10.1002/adma.202211609
M3 - Article
AN - SCOPUS:85159091091
SN - 0935-9648
JO - Advanced Materials
JF - Advanced Materials
ER -