Researchers reveal the crucial role of two mechano-sensing ion channels in preserving healthy stem cells.
A recent study conducted by The Hospital for Sick Children (SickKids) and Institut Curie has uncovered how stem cells perceive and react to their environments, which may have consequences for inflammatory bowel disease and colorectal cancer.
Stem cells are continuously adjusting to their surroundings to ensure the health of organs and tissues, responding to both chemical cues and physical forces. Dysfunctional stem cells can lead to various health issues, including inflammatory bowel disease (IBD) and colorectal cancer, where uncontrolled cell division can result in tumor formation.
Previously, the mechanisms by which stem cells perceive the physical forces in their surroundings were not well understood. However, new findings published in Science, driven by Dr. Meryem Baghdadi, a former postdoctoral researcher at SickKids, along with Dr. Tae-Hee Kim from SickKids and Dr. Danijela Vignjevic of Institut Curie, have shown that stem cells rely on two specific ion channels, known as PIEZO1 and PIEZO2, for their survival.
“The physical characteristics of the environment surrounding stem cells are vital for our overall health,” says Kim, a Senior Scientist in the Developmental & Stem Cell Biology program. “With this understanding, we can investigate strategies to enhance gastrointestinal regeneration, which could both prevent and repair damaged stem cells.”
Understanding how stem cells detect changes in the gut
Back in 2018, Dr. Xi Huang, another Senior Scientist in the Developmental & Stem Cell Biology program at SickKids, discovered that PIEZO ion channels play a role in tumor stiffness in brain cancer. Building on this finding, Kim’s team aimed to investigate how intestinal stem cells utilize PIEZO channels to remain healthy and function correctly.
In their preclinical studies, the team disabled (knocked out) PIEZO1 and PIEZO2 in the intestines. The outcomes were striking: without these PIEZO channels, the stem cells failed to perform essential functions, leading to severe health complications and rapid demise. Although previously regarded as having distinct roles, this study highlighted the surprising redundancy of these PIEZO channels in maintaining stem cell health.
The research teams of Kim and Vignjevic discovered that PIEZO ion channels assist stem cells in sensing physical changes in their environment, such as its stiffness or elasticity. In the absence of these channels, important signaling pathways were disrupted, causing stem cells to overlook critical environmental changes and differentiate incorrectly.
“When PIEZO channels are absent, stem cells can’t retain their identity and prematurely transform into different cell types, which leads to severe health issues,” explains Baghdadi.
This finding has major implications for human health, particularly for disorders characterized by abnormal stem cell activity, such as IBD, which is rapidly increasing in Canada, and bowel cancer, recognized as the third most prevalent cancer in the nation.
“We are increasingly unveiling that our cells are influenced by more than just biology; various chemical and mechanical signals drive cellular behavior,” observes Kim. “Understanding the mechanisms behind our body’s reactions to these signals could pave the way for groundbreaking research not only for gut health but across all aspects of health.”
This research was supported by the Canadian Institutes of Health Research (CIHR), the Labex Cell(n)Scale, the ARC Foundation, and the European Research Council (ERC). The lead authors express gratitude to their collaborators in Canada and Europe for their significant contributions.
