Terminally differentiated cells are regarded as the most stable and common cell state in adult organisms as they reside in growth arrest and carry out their cellular function. Improving our understanding of the mechanisms involved in promoting cell cycle exit would facilitate our ability to manipulate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, we demonstrated that a hyperosmolar environment enforced a protective p53-independent quiescent state in dedifferentiated hepatoma cells and pluripotent stem cells (PSCs)-derived models of human hepatocytes and endothelial cells, representing the endodermal and mesodermal lineages. Prolonged culture in hyperosmolar conditions stimulated transcriptional and functional cell maturation. Interestingly, hyperosmolar conditions did not only trigger cell cycle exit and cellular maturation but were also necessary to maintain this maturated state, as switching back to plasma osmolarity caused the loss of maturation markers and the gain of proliferative markers. Transcriptome analysis revealed activation of NF-κB and repression of WNT signaling as the two main pathways downstream of osmolarity-regulated growth arrest and cell maturation, respectively. This study revealed that increased osmolarity serves as a biochemical signal to promote long-term growth arrest, transcriptional changes, and maturation into different lineages, serving as a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.