Catalan researchers have found a new type of stem cells, known as quiescent, which are activated in case of need and have the power to generate all the cellular types of the intestine. They are relevant in tissue regeneration and for their involvement in tumors.
The intestine has a high rate of cellular regeneration due to the wear it suffers from degrading and absorbing of nutrients and removing unnecessary remains. Broadly speaking, its entire cell population is renewed once a week. This is why, the organ has a large volume of stem cells in constant division that are giving rise to various cell types that make up the intestine.
Scientists from the Institute for Research in Biomedicine (IRB Barcelona), led by Eduard Batlle, researcher at the Laboratory of Colorectal Cancer, presented in Cell Stem Cell a new group of stem cells of the intestine, with very different characteristics from the abundant and active stem cells already known in this organ. This new group is quiescent, that is, they do not proliferate and are in a state of apparent hibernation.
The experts, in collaboration with the National Center for Genomic Analysis (CNAG-CRG), describe this new group of cells as a reservoir of stem cells. They calculate there is an estimate of one quiescent stem cell per 10 active intestinal stem cells.
When an individual is healthy, these cells apparently have no relevant function. However, they are important in situations of stress, for example: following a chemotherapy treatment, in inflammation processes or tissue infections; conditions when the populations of active stem cells are excessively reduced. Its function would be to ensuring the regeneration of the organ giving rise to various cell types, repopulate the lost stem cells and restore balance to the tissue.
Eduard Batlle explains that discovering quiescent stem cells in the gut indicates that the biology of stem cells is more complex than previously known and breaks with the model of hierarchical cellular organization. “In the cellular hierarchy of the intestine, some cells are not above the other or vice versa, but the two populations are in continuous balance to ensure the proper functioning of the organ.”
Resistant to many forms of chemotherapy
Most anticancer drugs secondarily affect cells dividing in different tissues. “Quiescent stem cells, as they infrequently divide, are resistant to many forms of chemotherapy and regenerate the tissues that chemotherapy has damaged,” explains Batlle.
There are quiescent cells in many tissues, but they are not well known despite their relevance in regeneration processes and their possible involvement in tumors. “They are difficult to study, mainly because they are rare cells and there are technical limitations to follow them, to mark them and distinguish them from the others,” says Francisco Barriga, the first author of the paper and currently a postdoctoral researcher at the Memorial Sloan Kettering Cancer Center in New York (USA).
Thanks to advanced techniques such as the genetic tracing of cell lines and the analysis of the individual cell transcriptome by the CNAG-CRG and the Bioinformatics and Biostatistics Platform of IRB Barcelona, the group has identified the distinctive genetic program of quiescent stem cells from normal stem cells in the intestine; a work that has been developed in the last six years.
Researchers were able to track this cell population over time through a specific marker, the Mex3a protein. “Our intention is to continue researching quiescent stem cells in health and disease and to discover the function of the genes that distinguish them, both in the colon and in other organs,” concludes Batlle.