Protein protects embryonic stem cells' versatility and self-renewalMarch 24, 2008M. D. Anderson team connects REST to regenerative medicine, pediatric brain cancer HOUSTON - A protein known as REST blocks the expression of a microRNA that prevents embryonic stem cells from reproducing themselves and causes them to differentiate into specific cell types, scientists at The University of Texas M. D. Anderson Cancer Center report in the journal Nature. Researchers show RE1-silencing transcription factor (REST) plays a dual role in embryonic stem cells, said senior author Sadhan Majumder, Ph.D., professor in M. D. Anderson's Department of Cancer Genetics. "It maintains self-renewal, or the cell's ability to make more and more cells of its own type, and it maintains pluripotency, meaning that the cells have the potential to become any type of cell in the body." The paper posted online March 23 in advance of publication grew from M. D. Anderson research on the protein's role in medulloblastoma - an exceptionally aggressive pediatric brain cancer. Embryonic stem cells are essentially blank slates. They have the unique ability to develop from identical, unspecialized cells and then differentiate into distinct types of cells with special functions. In the laboratory, scientists have been able to induce embryonic stem cells to develop into heart muscle cells or insulin-producing cells of the pancreas. The hope is that embryonic stem cells might one day be used to restore or replace failing cells in the human body and perhaps treat a wide range of diseases. "Embryonic stem cells have a very high potential in medicine," Majumder said. "The critical thing is to learn the mechanisms that could be used to generate a lot of self-renewing embryonic stem cells and be able to differentiate them into various cell types." REST could play a key role in maintaining a steady supply of these cells and in preserving their differentiation capability. Suppressing MicroRNA-21 In studies using mouse embryonic stem cells, the researchers found that REST disarms a specific microRNA called microRNA-21 or miR-21. MicroRNAs are tiny pieces of RNA that control gene expression by binding to the gene's messenger RNA. The team found that MiR-21 suppresses embryonic stem cell self-renewal and is associated with a corresponding loss of expression of critical self-renewal regulators, such as Oct4, Nanog, Sox2 and c-Myc. REST counters this by suppressing miR-21 to preserve the cells' self-renewal and pluripotency. The researchers discovered the roles of REST and miR-21 in a series of experiments using cultured mouse embryonic stem cells in either a self-renewal state or a differentiating state. They found that REST expression was significantly higher in the self-renewal state. Withdrawing REST reduced the stem cells' ability to reproduce themselves and started differentiation - even when the cells were grown under conditions conducive to self-renewal. Adding REST to differentiating cells maintained their self-renewal. These experiments also revealed that REST is bound to the gene chromatin of a set of microRNAs with the potential to target self-renewal genes. REST controls transcription of 11 microRNAs. REST Implicated in Pediatric Brain Cancer Previous laboratory research suggests that the qualities that make REST beneficial in stem cell production and pluripotency may contribute to the development of medulloblastoma, an aggressive type of children's brain tumor. Medulloblastomas are believed to develop from undifferentiated neural stem cells in the external granule layer of the cerebellum. In earlier research, Majumder's group at M. D. Anderson discovered that about half of these tumors overexpress REST, which is not found in most neural cells. "We found that REST is a critical factor in this group of children's brain tumors," Majumder said, "and that its major function is to keep a group of specific brain stem cells, or progenitor cells, in a state of stemness." The researchers hypothesize that by maintaining the neural stem cells' 'stemness,' REST prevents their differentiation into normal and distinct types of cells, leading instead to tumor formation. The M. D. Anderson scientists are now exploring whether microRNAs might also play a role in medulloblastomas. Understanding REST function has applications in both medulloblastoma and embryonic stem cell biology. "Just as blocking REST function has therapeutic potential in medulloblastoma, blocking REST function to allow for differentiation of embryonic stem cells is a potentially critical step in regenerative medicine," Majumder said. University of Texas M. D. Anderson Cancer Center |
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| Related Embryonic Stem Cells Current Events and Embryonic Stem Cells News Articles Of mice and men: Stem cells and ethical uncertainties The recent creation of live mice from induced pluripotent stem cells (iPSCs) not only represents a remarkable scientific achievement, but also raises important issues, according to bioethicists at The Johns Hopkins University's Berman Institute of Bioethics. NIH-funded researchers transform embryonic stem cells into human germ cells Researchers funded in part by the National Institutes of Health have discovered how to transform human embryonic stem cells into germ cells, the embryonic cells that ultimately give rise to sperm and eggs. Placental precursor stem cells require testosterone-free environment to survive Trophoblast stem cells (TSCs), cells found in the layer of peripheral embryonic stem cells from which the placenta is formed, are thought to exhibit "immune privilege" that aids cell survivability and is potentially beneficial for cell and gene therapies. Endocrine Society calls for expanded scope and funding for stem cell research Stem cell research holds great promise for the treatment of millions of Americans with debilitating and possibly fatal diseases. Small mechanical forces have big impact on embryonic stem cells Applying a small mechanical force to embryonic stem cells could be a new way of coaxing them into a specific direction of differentiation, researchers at the University of Illinois report. Applications for force-directed cell differentiation include therapeutic cloning and regenerative medicine. Fate Therapeutics announces creation of small molecule platform for commercial-scale reprogramming Fate Therapeutics, Inc. announced today the generation of human induced-pluripotent stem cells (iPSCs) using a combination of small molecules that significantly improves the speed and efficiency of reprogramming. A major step in making better stem cells from adult tissue October 15, 2009 A team led by scientists from The Scripps Research Institute has developed a method that dramatically improves the efficiency of creating stem cells from human adult tissue, without the use of embryonic cells. New strategy for mending broken hearts? By mimicking the way embryonic stem cells develop into heart muscle in a lab, Duke University bioengineers believe they have taken an important first step toward growing a living "heart patch" to repair heart tissue damaged by disease. Liver cells grown from patients' skin cells Scientists at The Medical College of Wisconsin in Milwaukee have successfully produced liver cells from patients' skin cells opening the possibility of treating a wide range of diseases that affect liver function. Major improvements made in engineering heart repair patches from stem cells University of Washington (UW) researchers have succeeded in engineering human tissue patches free of some problems that have stymied stem-cell repair for damaged hearts. More Embryonic Stem Cells Current Events and Embryonic Stem Cells News Articles |
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