Researchers have discovered how stem cells perceive and respond to their environment.

Stem cells continuously adapt to their environment to maintain the health of organs and tissues, thanks to chemical signals and physical influences. When stem cells do not function properly, it can lead to a range of diseases, including inflammatory bowel disease (IBD) and colorectal cancer, as they continue to divide until a tumor is formed.

It has remained unclear how stem cells perceive the physical influences surrounding them, but new research findings published in the journal Science by lead researcher Dr. Meryem Baghdadi from SickKids Hospital, Dr. Tae-Hee Kim from SickKids, and Dr. Danijela Vignjevic from the Curie Institute have shown that the survival of stem cells depends on two ion channels known as PIEZO1 and PIEZO2.

“The physical properties of the environment around stem cells are critical for our health. With this knowledge, we will be able to explore ways to restore the gastrointestinal tract to not only prevent damage to stem cells but also to regenerate them,” said Tae-Hee Kim, a senior researcher in the Developmental Biology and Stem Cells program at SickKids.

How stem cells perceive changes in the intestine

In 2018, Dr. Xi Huang, a senior researcher in the Developmental Biology and Stem Cells program at SickKids, discovered that PIEZO ion channels affect tumor stiffness in brain cancer. Inspired by this research, Kim's research team decided to investigate how intestinal stem cells utilize PIEZO channels to maintain health and proper functioning.

In a preclinical model, the research team disabled (blocked) the PIEZO1 and PIEZO2 channels in the intestine. The results were striking: in the absence of both PIEZO channels, stem cells could not sustain their necessary functions, leading to severe diseases and rapid death. While it was previously known that PIEZO channels serve different functions, this study revealed their unexpected additional role in maintaining stem cells.

In the lab, Kim and Vignjevic established that PIEZO ion channels help stem cells sense physical changes in their environment, such as its stiffness or stretchability. Without these channels, the balance in two critical signaling pathways was disrupted, causing stem cells to overlook important changes in their surroundings and differentiate incorrectly.

In the absence of PIEZO channels, stem cells cannot remain stem cells. Instead, they transition too quickly into other cell types, resulting in significant health issues.

This discovery is of great importance for human health, particularly for diseases with abnormal stem cell activity, such as IBD, which is one of the fastest-growing diseases globally, and colorectal cancer, the third most common cancer.

Researchers are increasingly convinced that our cells are not just a biological system, but also a system of chemical and mechanical signals that govern cell activity. Understanding how and why our body responds to these signals opens up new research opportunities not only for gut health but for all aspects of human health.