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Master regulatory gene of epithelial stem cells identified
May 04, 2007Findings have implications for adult stem cell renewal & prostate, breast and skin cancers
BOSTON -- The skin's ability to replace the tissue it sloughs off is controlled by a variety of genes. A new study from Harvard Medical School published in the May 4 issue of Cell, however, identifies a "master regulator" of this regeneration process not only for skin, but for many epithelial tissues including breast, prostate, and urogenital tract. This master regulator of epithelial stem cells turns out to be the p63 gene, a close relative to the well-known tumor-suppressing p53 gene. Without p63, mutant mice run out of the regenerative epithelial stem cells. The findings also have implications for cancers of the skin, breast and prostate, which are among the most common human malignancies.
The role of p63 in epithelial stem cells has been controversial. Some studies found that p63 maintains a steady pool of the regenerative cells, while other studies argued that p63 has more to do with causing the cells to differentiate into particular types of tissue. The study, which was lead by Frank McKeon, PhD, professor of cell biology at Harvard Medical School (HMS), shows that p63's role in not in tissue differentiation but rather to impart "stemness" to the regenerative cells in these tissues.
"With the p63-lacking mice you get normal commitment and differentiation," says McKeon. "The defect is simply running out of stem cells. When you run out of stem cells, you run out of those tissues as we have seen with the mice lacking the p63 gene."
Having established that p63 was only important to the maintenance of stem cells, McKeon and his research team then used the epithelial stem cell cloning methods developed by Howard Green, MD, the George Higginson professor of cell biology at HMS, to show that p63's key function was to provide the enhanced potential of stem cells to divide.
"The fact that p63 is essential for these epithelial stem cells, while other master regulators have been identified for blood stem cells and spermatocyte stem cells, suggests a fundamental requirement for tissue specificity of these regulators that we don't understand," says McKeon. "Dissecting the genetic programs controlled by these regulators will tell us much about how stem cells function and how they go awry in cancer."
Harvard Medical School
"With the p63-lacking mice you get normal commitment and differentiation," says McKeon. "The defect is simply running out of stem cells. When you run out of stem cells, you run out of those tissues as we have seen with the mice lacking the p63 gene."
Having established that p63 was only important to the maintenance of stem cells, McKeon and his research team then used the epithelial stem cell cloning methods developed by Howard Green, MD, the George Higginson professor of cell biology at HMS, to show that p63's key function was to provide the enhanced potential of stem cells to divide.
"The fact that p63 is essential for these epithelial stem cells, while other master regulators have been identified for blood stem cells and spermatocyte stem cells, suggests a fundamental requirement for tissue specificity of these regulators that we don't understand," says McKeon. "Dissecting the genetic programs controlled by these regulators will tell us much about how stem cells function and how they go awry in cancer."
Harvard Medical School
Stem Cells Current Events and Stem Cells News RSSFirst reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
The use of stem cells in regenerative medicine may also be detrimental for health
The use of stem cells in regenerative medicine is not always beneficial for human health, it may even be harmful according to a work done by the University of Granada and University of León. Scientists have demonstrated that transplantation of human mononuclear cells isolated from umbilical cord blood exerted a deleterious effect in rats with liver cirrhosis.
Penn Study Provides First Clear Idea of How Rare Bone Disease Progresses
An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the body's skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.
Iowa State University researcher discovers key to vital DNA, protein interaction
A researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances."
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
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