Volumetric Compression Induces Intracellular Crowding to Control Intestinal Organoid Growth via Wnt/β-Catenin Signaling
Author(s)
Li, Yiwei; Chen, Maorong; Hu, Jiliang; Sheng, Ren; Lin, Qirong; He, Xi; Guo, Ming; ... Show more Show less
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© 2020 Elsevier Inc. Enormous amounts of essential intracellular events are crowdedly packed inside picoliter-sized cellular space. However, the significance of the physical properties of cells remains underappreciated because of a lack of evidence of how they affect cellular functionalities. Here, we show that volumetric compression regulates the growth of intestinal organoids by modifying intracellular crowding and elevating Wnt/β-catenin signaling. Intracellular crowding varies upon stimulation by different types of extracellular physical/mechanical cues and leads to significant enhancement of Wnt/β-catenin signaling by stabilizing the LRP6 signalosome. By enhancing intracellular crowding using osmotic and mechanical compression, we show that expansion of intestinal organoids was facilitated through elevated Wnt/β-catenin signaling and greater intestinal stem cell (ISC) self-renewal. Our results provide an entry point for understanding how intracellular crowdedness functions as a physical regulator linking extracellular physical cues with intracellular signaling and potentially facilitate the design of engineering approaches for expansion of stem cells and organoids.
Date issued
2021Department
Massachusetts Institute of Technology. Department of Mechanical EngineeringJournal
Cell Stem Cell
Publisher
Elsevier BV
Citation
Li, Yiwei, Chen, Maorong, Hu, Jiliang, Sheng, Ren, Lin, Qirong et al. 2021. "Volumetric Compression Induces Intracellular Crowding to Control Intestinal Organoid Growth via Wnt/β-Catenin Signaling." Cell Stem Cell, 28 (1).
Version: Author's final manuscript