Leave stem cells embryonic
How to prevent a stem cell from differentiating
LifeSciencesToday based on UCSD materials: Keeping Stem Cells Pluripotent
Stem cells are the raw material of the body. These are the cells from which all other cells with specialized functions are created. Under certain conditions in the body or in the laboratory, stem cells divide to form daughter cells that can become either new stem cells (self-renewal) or specialized cells (differentiation) with a more specific function, such as blood cells, brain cells, heart muscle or bone. Stem cells are unique – no other cell in the body has the natural ability to form new cell types. (Fig. allthingsstemcell.com )By blocking the key signal, the scientists kept the embryonic stem cells in an undifferentiated state
Although the ability of human embryonic stem cells (CESCS) to become mature cells of any type – from a neuron to a cardiomyocyte, fibroblast or osteoblast – is undoubtedly crucial for the development of the human body, no less important is the mechanism of retaining CESCS in a pluripotent state until the moment when this transformation becomes necessary.
In an article published in the online publication PNAS (Fernandez et al., The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells), scientists from the School of Medicine of the University of California at San Diego (University of California, San Diego School of Medicine) identified the receptor of one of the key genes and a signaling pathway important for maintaining the undifferentiated state of human ESCs.
This discovery sheds new light on the fundamental biology of human ESCs with their enormous potential as a therapeutic tool and offers a new target for attacking cancer stem cells, which, in their unrestrained destructive growth, apparently rely on this receptor and pathway.
The study, led by Karl Willert, PhD, associate professor of the Department of Cellular and Molecular Medicine, focuses on the role of the highly conserved Wnt signaling pathway – a large family of proteins long recognized as the most important regulator of stem cell self–renewal - and, in particular, on the encoded receptor known as the Frizzled family receptor 7, or FZD7.
The canonical Wnt signaling pathway mediates its action by binding to its Frizzled receptors (FZD) and co-receptors, LRP5/6. This causes activation of intracellular Dishevelled (Dvl), which, in turn, inhibits the enzyme glycogen synthase kinase-3beta (glycogen synthase kinase-3beta, GSK3beta). This leads to stabilization and translocation into the beta-catenin nucleus, inducing gene transcription through the LEF/TCF family of transcription factors. In the absence of Wnt signaling, the complex containing GSK3beta phosphorylates beta-catenin, which leads to its degradation by ubiquitination. Wnt signaling is involved in maintaining stem cells in an undifferentiated state, however, it is often unclear which of the Wnts and Wnt receptors mediates this function. American scientists have studied the role of the Wnt FZD7 receptor in maintaining human ESCs in an undifferentiated and pluripotent state. Compared with populations of differentiated cells, the expression of FZD7 in undifferentiated cells is significantly increased, and the prevention of its expression or function either by a knockdown mediated by a short hairpin RNA, or by an antigen-binding fragment (fab) molecule directed against FZD7 removes the cESC from a pluripotent state. FZD7-specific fab blocks signaling via the Wnt3a protein by reducing FZD7 protein levels, suggesting that FZD7 transduces Wnt signals to activate Wnt/beta-catenin signaling. These results show that FZD7 encodes a pluripotent state regulator and that endogenous Wnt/beta-catenin signaling via FZD7 is required to preserve the undifferentiated phenotype of human ESCs. (Fig. bioscience.org )"Wnt signaling via FZD7 is necessary to maintain the undifferentiated state of human ESCs," explains Dr. Willert.
"If you block the FZD7 function, thereby interfering with the Wnt path, the CESCS come out of an undifferentiated and pluripotent state."
The researchers proved this with the help of a protein with antibody properties that binds to FZD7, preventing its function from being realized.
"If the FZD7 function is blocked by this FZD7-specific compound, human ESCs can no longer receive the Wnt signal required to maintain their undifferentiated state."
FZD7 is a so-called "oncophetal protein" expressed only during embryonic development and by some human tumors. Other studies have shown that FZD7 can be a marker of cancer stem cells and plays an important role in stimulating tumor growth. If this is the case, Dr. Willert believes, a violation of the function of FZD7 in cancer cells is likely to hinder their development and growth in the same way as it occurs in human ESCs.
Dr. Willert and his colleagues, including University of California San Diego Professor Emeritus Dennis Carson, MD, of the Sanford Consortium for Regenerative Medicine, plan to continue testing the FZD7-blocking compound as a potential cancer drug.
Portal "Eternal youth" http://vechnayamolodost.ru20.01.2014