Dynamic switching between revival stem cells and conventional intestinal stem cells enables efficient tissue repair without exhausting the stem cell pool, report researchers from Institute of Science Tokyo. Using organoid and mouse disease models, the researchers uncovered how flexible stress-tolerant cell states contribute to intestinal repair—providing a better understanding of the biological mechanisms driving intestinal regeneration.
All living tissues have the ability to repair themselves after injury, infection, or inflammation to maintain normal function. This is especially important in the intestine, where the epithelial lining is constantly exposed to damage and stress. The lining is sustained by conventional stem cells, known as crypt base columnar cells (CBCs), located at the base of finger-like structures called villi. As these stem cells divide and move upward, they develop into mature cells such as enterocytes (nutrient-absorbing cells). Although this continuous renewal process is well known, how the intestine regenerates efficiently without depleting its stem cell reserve has remained unclear.
Addressing this gap, a team of researchers from Institute of Science Tokyo (Science Tokyo), Japan, led by Associate Professor Shiro Yui from the Center for Stem Cell and Regenerative Medicine, Institute of Biomedical Engineering, Science Tokyo, along with graduate student Dr. Sakura Kirino of the Department of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Science Tokyo (supervised by Professor Ryuichi Okamoto), conducted a detailed investigation into the origin and biological role of “revival stem cells,” transient cell states that emerge during intestinal repair.
The study was conducted in collaboration with Professor Hans Clevers from the Hubrecht Institute, the Netherlands, Professor Daisuke Ban from the Department of Hepatobiliary and Pancreatic Surgery, Science Tokyo, Associate Professor Kensuke Miyake from the Institute of Integrated Research, Science Tokyo, and Professor Mamoru Watanabe, Director of the Organoid Center, Juntendo University, Japan. The findings of the study were published in Volume 9 of the journal Communications Biology on January 13, 2026.
“We wanted to understand how intestinal tissues regenerate efficiently without compromising long-term stem cell maintenance,” says Kirino. “Surprisingly, we discovered a unique mechanism in which conventional stem cells can temporarily switch into a specialized regenerative state and later return to their original identity.”
The specialized regenerative state is represented by “revival stem cells” (which emerge from conventional stem cells in response to tissue damage). This process of conversion is called fetal reversion. The revival stem cells exhibit enhanced tolerance to stress, which allows them to survive and regenerate even in damaged tissue environments.
Using unique intestinal organoids (lab-grown tissue models) and mouse models of colitis, the team demonstrated that revival stem cells can be induced from multiple intestinal cell types, including both conventional CBCs and differentiated enterocytes. Additionally, they observed that the conversion between revival stem cells and conventional stem cells was bidirectional, suggesting that regeneration depends on dynamic cellular interconversion rather than on a fixed hierarchy.
Overall, the study explains the link between two mechanisms of plasticity, namely fetal reversion and spatial plasticity. Spatial plasticity explains the conversion of differentiated cells back to CBCs, whereas fetal reversion explains the reversible conversion between CBCs and revival stem cells. According to the study, fetal reversion may act as the entry point to spatial plasticity. When the intestinal lining is damaged, differentiated cells first become stress-resistant revival stem cells. After repair, these cells convert into CBCs, replenishing the stem cell pool and supporting efficient regeneration.
By deepening the scientific understanding of intestinal epithelial regeneration, the study opens new avenues for investigating diseases characterized by impaired regeneration. In particular, the findings are expected to contribute to ongoing efforts to elucidate the pathology of inflammatory bowel disease and colorectal cancer, which have attracted intense global research interest. “The discovery provides a new direction for understanding how tissues recover from damage. With further research, it may ultimately help uncover novel strategies for treatment and prevention of chronic intestinal disorders,” Yui concludes.
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About Institute of Science Tokyo (Science Tokyo)
Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”
Communications Biology
Experimental study
Cells
Fetal reversion from diverse lineages sustains the intestinal stem cell pool and confers stress resilience
13-Jan-2026
Hans Clevers is inventor on several patents related to organoid technology. His full disclosure can be found at https://www.uu.nl/staff/JCClevers. All other authors declare no competing interests.