Professor Jiwon Jang and Seungbok Yang, a PhD candidate, from the Department of Life Sciences at Pohang University of Science and Technology (POSTECH), and Dr. Mahdi Golkaram from the Department of Mechanical Engineering at University of California Santa Barbara (UCSB) have discovered a new way that cells respond to mechanical cues. Their findings were published on May 3 in the online edition of Nature Cell Biology, an international journal in the field of cell biology.
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Historically, much of the focus in cell biology research has been on understanding how cells respond to chemical signals, such as diffusible signaling molecules. However, it has been discovered that cells also react to mechanical stimuli, including cell density, size, and substrate stiffness, by expressing specific genes. Despite this, the mechanisms by which cells perceive mechanical stimuli have not been thoroughly investigated.
This study utilized human embryonic stem cells (hESCs) to explore how cells detect and respond to mechanical signals. By analyzing the transcriptome of hESCs grown under varying cell densities, sizes, and substrate stiffness, the researchers aimed to uncover the mechanisms involved in this process.
In their study, the researchers identified a key player called “ETV4” that is responsible for regulating changes in stem cell density and controlling differentiation.
Additionally, the team uncovered the complex process by which ETV4 detects mechanical signals. Initially, integrin receptors1 detect changes in cell density, which then affects the endocytosis of a cell surface receptor known as Fibroblast Growth Factor Receptor (FGFR). The mechanical regulation of FGFR endocytosis determines the protein stability of ETV4 through ERK signaling.
ETV4 also plays a role in directing stem cell differentiation.The researchers found that mesendoderm formation is favored in regions with lower cell density, while neuroectoderm development is promoted in areas with higher cell density. They also identified a new mechanotransducer, ETV4, which connects cell density changes to stem cell differentiation. Professor Jiwon Jang from POSTECH, who led the study, emphasized the significance of mechanical cues in regulating stem cell differentiation and the key role of ETV4. He is hopeful that this discovery can be used to develop technologies for controlling the differentiation of stem cells, especially in relation to ETV4’s implications as a critical oncogene.The study investigated how mechanical cues can impact the behavior of cancer cells. The research received funding from several programs of the National Research Foundation of Korea, including the Biomedical Technology Development Program, the Basic Research Program for Individuals, the Group Research and Basic Research Lab Program, and the Smart Specialization Infrastructure Project.A transmembrane receptor plays a role in connecting cells to the extracellular matrix and is responsible for transmitting physical and chemical changes inside and outside the cell for signal transduction in both directions
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