From lung to gut - the Wnt signaling pathway transforms cell fateJune 03, 2004Researchers have uncovered a cellular mechanism that can alter the fate of progenitor cells that normally generate the lung, causing them to create gut cells instead. The findings, which are published this week in the top-tier Open Access journal, Journal of Biology, could help researchers hoping to use adult stem cells for therapeutic purposes. Brigid Hogan and Tadashi Okubo, from Duke University Medical Center, studied the lungs of transgenic mice that had developed under the influence of artificially high levels of activity in the Wnt signaling pathway, caused by the presence of an activated beta catenin gene. They found that although externally the lungs looked normal, the interior of the lungs had lost the normal branching tree-like structure lined with rounded alveolar cells. Instead, a few wide bronchial tubes opened directly into large sacs that were lined with a rapidly proliferating cuboidal epithelium. Looking more closely at these epithelial cells, the researchers found that many of them were not expressing genes typical of lung cells, such as the genes encoding secretoglobin and surfactants. In addition, microarrays comparing the transgenic cells with normal lung epithelial cells showed a general reduction in the expression of lung-specific genes and a strong expression, instead, of genes characteristic of intestinal cells. "A striking feature of the microarray data was the high expression in transgenic lungs of genes normally associated with the specification and differentiation of gut secretory cell lineages," say Hogan and Okubo. These included the gene encoding the Atoh1 transcription factor, which is normally turned off in lung cells. "In particular there was a very high level of expression of genes characteristic of Paneth cells, which are normally found in the base of crypts in the small intestine," they continue. Signaling downstream of beta catenin normally occurs in cells that have been activated by molecules of the Wnt family. Wnts are known to play a role in the development of the gut, and their presence in developing lungs suggests that they also function in lung development. Wnts also control cell fate in cells of the epidermis and hair follicle. "These results show that hyperactive Wnt signaling in lung progenitor cells can induce a dramatic shift in lineage commitment and the generation of intestinal cell types," write the authors. Understanding the mechanism by which these progenitor cells can switch their fate and create other tissues of the same embryonic origin could be of great importance to researchers working with adult stem cells, who would like to program cells to adopt particular fates. The research could also shed light on a condition known as Barrett's esophagus, where patches of the esophagus lining alter to resemble the lining of the intestine - a process known as intestinal metaplasia. Hogan and Okubo believe that there is a possibility that "elevated Wnt signaling in adult stem cells or progenitor cells is at least one factor promoting intestinal metaplasia in humans." | |||||||||||||||||||||
|
Related Stem Cells Current Events and Stem Cells News Articles Scientists can now differentiate between healthy cells and cancer cells One of the current handicaps of cancer treatments is the difficulty of aiming these treatments at destroying malignant cells without killing healthy cells in the process. Testes stem cell can change into other body tissues, Stanford/UCSF study shows Scientists at the Stanford University School of Medicine and at UC-San Francisco have succeeded in isolating stem cells from human testes. Salk researchers develop novel glioblastoma mouse model Researchers at the Salk Institute for Biological Studies have developed a versatile mouse model of glioblastoma-the most common and deadly brain cancer in humans-that closely resembles the development and progression of human brain tumors that arise naturally. Hebrew University scientists succeed through stem cell therapy in reversing brain birth defects Scientists at the Hebrew University of Jerusalem have succeeded in reversing brain birth defects in animal models, using stem cells to replace defective brain cells. Biomedical researchers create artificial human bone marrow in a test tube Artificial bone marrow that can continuously make red and white blood cells has been created in a University of Michigan lab. Bioreactors might solve blood-platelet supply problems It might be possible to grow human blood platelets in the laboratory for transfusion, according to a new study at The Ohio State University Medical Center. Patient-derived induced stem cells retain disease traits hen neurons started dying in Clive Svendsen's lab dishes, he couldn't have been more pleased. The dying cells - the same type lost in patients with the devastating neurological disease spinal muscular atrophy - confirmed that the University of Wisconsin-Madison stem cell biologist had recreated the hallmarks of a genetic disorder in the lab, using stem cells derived from a patient. Molecular marker identifies normal stem cells as intestinal tumor source Scientists at St. Jude Children's Research Hospital have answered a central question in cancer biology: whether normal stem cells can give rise to tumors. Study of placenta unexpectedly leads to cancer gene University of Rochester Medical Center scientists discovered a gene mutation that impairs the placenta and also is influential in cancer development, according to a study published online December 16, 2008, in the journal PLoS (Public Library of Science) Biology. Heart regenerates after infarction -- first trials with mice Up until today scientists assumed that the adult heart is unable to regenerate. Now, researchers and cardiologists from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and the Charité - Universitätsmedizin Berlin (Germany) have been able to show that this dogma no longer holds true. More Stem Cells Current Events and Stem Cells News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||