Breakthrough in Gut Stem Cell Research: Misidentification Corrected After 15 Years


Recent research from Columbia University has revealed a significant misidentification of gut stem cells that has impacted regenerative medicine research and treatments for the past 15 years. The studies, published in the journal Cell, have identified the true gut stem cells in a different region of the gut, which holds promise for new advancements in treating intestinal diseases and beyond.

The Discovery of True Gut Stem Cells

Scientists at Columbia University, through two independent studies, have discovered that the actual stem cells in the gut are located in the isthmus region, not the crypts as previously believed. This misidentification has potentially hindered progress in regenerative medicine for over a decade. The new findings could pave the way for more effective therapies targeting intestinal diseases and other medical conditions.

The Misidentification and Its Impact

For the past 15 years, research on gut stem cells has been based on the belief that Lgr5+ cells located at the bottom of the intestinal crypts were the true stem cells. This belief was widely accepted following a landmark study in 2007. However, recent lineage tracing and computational tools have shown that these cells are descendants of the true stem cells, which are actually located in the isthmus region.

The misidentification has significant implications for regenerative medicine, as understanding the true nature of gut stem cells is crucial for developing effective treatments. The new discovery challenges the long-held model and suggests that previous research may need to be reevaluated.

The Role of Gut Stem Cells

Gut stem cells are essential for maintaining the intestinal lining, which is a single layer of cells responsible for digesting food, absorbing nutrients, and fighting microbes. These cells are among the hardest working in the body, continuously replenishing the intestinal lining every four days. Accurate identification of these stem cells is vital for understanding their role in tissue regeneration and for developing therapies for various diseases.

Uncovering the True Stem Cells

The Columbia research teams, led by Timothy Wang and Kelley Yan, used advanced computational algorithms and single-cell RNA sequencing to characterize cells in the intestinal crypts. Their analysis revealed that the true stem cells are located in the isthmus region, marked by a protein called FGFBP1. These FGFBP1+ cells give rise to all intestinal cells, including the previously believed Lgr5+ cells.

The researchers employed time-resolved fate mapping, a technique that allowed them to track cell lineage over time. This technique confirmed that FGFBP1+ cells are the true stem cells, contradicting the accepted model that Lgr5+ cells are the primary stem cells in the gut.

Implications for Regenerative Medicine

This discovery has the potential to revolutionize the field of regenerative medicine. By accurately identifying the true stem cells, researchers can develop targeted therapies for intestinal diseases and possibly other organs. The findings also suggest that some cancers may arise from these stem cells, opening the door to novel cancer treatments.

The implications extend beyond the gut, as understanding the universal pathways of stem cells could lead to breakthroughs in treating other tissues, such as the heart, lungs, brain, and more. The accurate identification of stem cells is critical for the success of regenerative medicine and the development of effective therapies.

Supporting Studies and Future Directions

The studies conducted by Columbia scientists were supported by various grants from the U.S. National Institutes of Health and other funding sources. The research teams included numerous experts from Columbia and other institutions, highlighting the collaborative effort behind this groundbreaking discovery.

The findings have been published in two papers: “Time-resolved fate mapping identifies the intestinal upper crypt zone as an origin of Lgr5+ crypt base columnar cells” and “Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury.” These studies provide a comprehensive analysis of the new stem cell model and its implications for regenerative medicine.


The identification of the true gut stem cells in the isthmus region marks a significant advancement in regenerative medicine. This discovery challenges the long-held belief that Lgr5+ cells are the primary stem cells in the gut, offering new insights into the nature of stem cells and their role in tissue regeneration. The findings have the potential to improve therapies for intestinal diseases and beyond, paving the way for new advancements in medical research and treatment.

By accurately identifying the true stem cells, researchers can develop targeted therapies that may revolutionize the field of regenerative medicine and lead to breakthroughs in treating various diseases. This discovery highlights the importance of precise identification in scientific research and its profound impact on developing effective treatments for medical conditions.

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