Silenced gene in worm shows role in regenerationNovember 28, 2005When smedwi-2 gene is silenced, regeneration stopped in planarians SALT LAKE CITY - Researchers at the University of Utah have discovered that when a gene called smedwi-2 is silenced in the adult stem cells of planarians, the quarter-inch long worm is unable to carry out a biological process that has mystified scientists for centuries: regeneration. The study published in the Nov. 25 issue of Science was led by Alejandro Sánchez Alvarado, Ph.D., Howard Hughes Medical Institute investigator and professor of neurobiology and anatomy at the U of U School of Medicine, and carried out by members of his laboratory, in particular Helen Hay Whitney Foundation post-doctoral fellow Peter W. Reddien who is now an Associate Member at the Whitehead Institute for Biomedical Research. Elimination of smedwi-2 not only leads to an inability to mount a regenerative response after amputation, but also to the eventual demise of unamputated animals along a reproducible series of events, that is, regression of the head tip, curling of the body and tissue disintegration. These defects are very similar to what is observed after the planarian stem cells are destroyed by lethal doses of irradiation. The key difference, however, is that the irradiation-like defects observed in animals devoid of smedwi-2 occur even though the stem cells are still present in the organism.
This finding suggests something surprising: the instructions that a daughter stem cell needs to differentiate for regeneration or for maintaining tissue structure begin to be defined at the time of division of its parent cell. "Once the smedwi-2 molecule is eliminated, the animal is destined to die since the functions of the daughter cells are severely compromised" said Sánchez Alvarado. The study follows a landmark work that he and Reddien published last spring in Developmental Cell, in which, using a method of gene silencing called RNA interference (RNAi), the researchers silenced more than 1,000 planarian genes, some of which they identified as essential for regeneration. The Science study focus on one such gene, smedwi-2, and brings a new level of genetic detail to understanding planarian regeneration. Planarians long have fascinated biologists with their ability to regenerate. A worm sliced in two forms two new worm s; even a fractional part of a planarian will grow into a new worm. Scientists know that planarian stem cells, called neoblasts, are central to regeneration, but their exact role is only now being learned. When an animal stem cell divides, two daughter cells are formed: one that is another stem cell and a second one that can differentiate into the cells that form bone, tissue, and other parts of an organism. These second types of cells are essential for regeneration or maintaining the form and function of tissues by replacing cells that die, a process called homeostasis. By eliminating smedwi-2, the researchers uncovered a role of this protein in regulating the normal differentiation and function of daughter cells. The researchers postulated three theories why the worms could not regenerate or maintain cells after smedwi-2 was silenced: - The stem cells were not responding to tissue damage or homeostasis signals. - The stem cell division progeny failed to migrate to the appropriate tissues. - The daughter cells didn't know how to differentiate. The team found that the stem cells were competent to robustly respond to amputation by significantly increasing their proliferation as well as to home to tissues undergoing homeostasis. But the researchers also found that once the daughter cells reach their target tissues, they were unable to properly differentiate. "The smedwi-2 molecule is doing something early in the specification of stem cell progeny that modulates their ability to differentiate into the proper cell type," Sánchez Alvarado said. How this molecule is modulating stem cells is one of the next steps that he and Reddien are trying to solve. The answer could have far-reaching implications, because genes similar to smedwi-2 are found in plants, animals and human beings. University of Utah Health Sciences Center | |||||||||||||||||||||
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Related Regeneration News Articles Hearing restoration may be possible with cochlear repair after transplant of human cord blood cells According to an Italian research team publishing their findings in the current issue of Cell Transplantation (17:6), hearing loss due to cochlear damage may be repaired by transplantation of human umbilical cord hematopoietic stem cells (HSC) since they show that a small number migrated to the damaged cochlea and repaired sensory hair cells and neurons. Cardiac cell transplant studies show promise in cardiac tissue repair Two studies published in the current issue of CELL TRANSPLANTATION (17:6) examine the efficacy of transplanting bone marrow cells (BMCs) for the repair of heart tissue. Bone marrow stem cells may help control inflammatory bowel disease Massachusetts General Hospital (MGH) investigators have found that infusions of a particular bone marrow stem cell appeared to protect gastrointestinal tissue from autoimmune attack in a mouse model. Hydrogels provide scaffolding for growth of bone cells Hyaluronic hydrogels developed by Carnegie Mellon University researchers may provide a suitable scaffolding to enable bone regeneration. The hydrogels, created by Newell Washburn, Krzysztof Matyjaszewski and Jeffrey Hollinger, have proven to encourage the growth of preosteoblast cells, cells that aid the growth and development of bone. Doctoral student Sidi Bencherif will present this research, Sunday, Aug. 17 at the 236th national meeting of the American Chemical Society in Philadelphia. Vine invasion? UWM ecologist looks at coexistence of trees and lianas Among the hundreds of species of woody vines that University of Wisconsin-Milwaukee ecologist Stefan Schnitzer has encountered in the tropical forests of Panama, the largest has a stalk nearly 20 inches in circumference. Sugar study is sweetener for stem cell science Scientists at The University of Manchester are striving to discover how the body's natural sugars can be used to create stem cell treatments for heart disease and nerve damage - thanks to a £370,000 funding boost. MIT identifies cells for spinal-cord repair A researcher at MIT's Picower Institute for Learning and Memory has pinpointed stem cells within the spinal cord that, if persuaded to differentiate into more healing cells and fewer scarring cells following an injury, may lead to a new, non-surgical treatment for debilitating spinal-cord injuries. Stem cell chicken and egg debate moves to unlikely arena: the testes Logic says it has to be the niche. As air and water preceded life, so the niche, that hospitable environment that shelters adult stem cells in many tissues and provides factors necessary to keep them young and vital, must have emerged before its stem cell dependents. Myostatin inhibitors may improve recovery of wartime limb injuries Inhibiting a growth factor that keeps muscles from getting too big may optimize recovery of injured soldiers, researchers say. Novel hydrogel systems for dentin regeneration Dental caries, or tooth decay, continues to be the most prevalent infectious disease in the world, presenting significant public health challenges and socio-economic consequences. More Regeneration News Articles |
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