Professor Jiwon Jang and Seungbok Yang, PhD candidate, from the Department of Life Sciences, Pohang University of Science and Technology (POSTECH), and Dr. Mahdi Golkaram from the Department of Mechanical Engineering, University of California, Santa Barbara (UCSB) have discovered a new regulator that governs how cells respond to mechanical signals. Their findings were published May 3 in the online edition of nature cell biologyan international journal in the field of cell biology.
Much research in cell biology has traditionally focused on understanding how cells react to chemical signals, such as diffusible signaling molecules. However, cells also respond to mechanical stimuli such as density, size, and stiffness of the cell substrate by expressing specific genes. However, the mechanisms by which mechanical regulators perceive mechanical stimuli have remained largely unexplored.
In this research, the researchers used human embryonic stem cells (hESCs) to delve deeper into how the cells detect and react to mechanical signals. By examining the transcriptome of hESCs cultured under different cell densities, the researchers identified a key player known as “ETV4,” responsible for mediating variations in stem cell density and controlling differentiation.
Additionally, the team deciphered the intricate mechanism through which ETV4 perceives mechanical signals. Initially, the integrin receptors1 recognize alterations in cell density, subsequently modulating the endocytosis of a cell surface receptor, the fibroblast growth factor receptor (FGFR). Mechanical regulation of FGFR endocytosis determines ETV4 protein stability through ERK signaling.
During the stem cell differentiation process, ETV4 plays a role in directing mesendoderm formation in regions characterized by low cell density, while promoting neuroectoderm development in areas of high cell density. The researchers discovered that a novel mechanotransducer ETV4 links cell density dynamics to stem cell differentiation.
POSTECH Professor Jiwon Jang, who led the research, said: “We have discovered the importance of mechanical signals in regulating stem cell differentiation along with the critical involvement of ETV4.” He expressed optimism by saying, “Given the substantial implications of ETV4 as a critical oncogene, we envision harnessing this idea to devise technologies aimed at controlling cancer cells through mechanical signals.”
The research was carried out with support from the Biomedical Technology Development Program, the Basic Research Program for Individuals, the Basic Research Laboratory and Group Research Program, and the Intelligent Specialization Infrastructure Project of the National Research Foundation. from Korea. The research was carried out with the support of the Biomedical Technology Development Program, the Basic Research Program for Individuals, the Basic Research Laboratory and Group Research Program, and the Intelligent Specialization Infrastructure Project of the National Foundation of Korea Research.
1. Integrin receptor: A transmembrane receptor that facilitates connections of the cell with the extracellular matrix and participates in intracellular signal transduction by transmitting physicochemical changes inside and outside the cell in both directions.