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Archive - Jan 28, 2014 - Story

Scientists ID Protein Crucial to the First Step of Cilium Formation, May Aid Understanding of Ciliopathies Like PKD

A team of researchers from Penn State University and the University of California-San Francisco has discovered a protein that is required for the growth of tiny, but critical, hair-like structures called cilia on cell surfaces. The discovery has important implications for human health because lack of cilia or problems with them can lead to serious diseases such as polycystic kidney disease PKD), blindness, and neurological disorders. "If we want to better understand and treat diseases related to cilium development, we need to identify important regulators of cilium growth and learn how those regulators function," said co-author Dr. Aimin Liu, Associate Professor of Biology at Penn State. "This work gives us significant insight into one of the earliest steps in cilium formation." The researchers describe their findings in a paper that was published online on January 27, 2014 in PNAS. In addition to Dr. Liu, article authors include Penn State cellular biologists Dr. Xuan Ye, Dr. Huiqing Zeng, and Dr. Gang Ning, as well as Dr. Jeremy F. Reiter, a biophysicist at the University of California-San Francisco. Cilia, which are present on the surface of almost all mammalian cells, are responsible for sending, receiving, and processing information within the body. "You could think of cilia as the cells' antennae," Dr. Liu said. "Without cilia, the cells can't sense what's going on around them, and they can't communicate." Cilia also perform important filtering and cleansing functions. For example, cilia inside the trachea, or windpipe, trap and prevent bacteria from entering the lungs. In a previous study, Dr. Liu and his colleagues learned that a protein called C2cd3 is important for cilium formation because mice that lacked this protein exhibited severe developmental problems typically associated with the lack of cilia.

Gone Today, Hair Tomorrow !

One potential approach to reversing hair loss uses stem cells to regenerate the missing or dying hair follicles. But it hasn't been possible to generate sufficient number of hair-follicle-generating stem cells – until now. Xiaowei "George" Xu, M.D., Ph.D., Associate Professor of Pathology and Laboratory Medicine and Dermatology at the Perelman School of Medicine, University of Pennsylvania (Penn), and colleagues published online on January 26, 2014 in Nature Communications a method for converting adult cells into epithelial stem cells (EpSCs), the first time anyone has achieved this in either humans or mice. The epithelial stem cells, when implanted into immunocompromised mice, regenerated the different cell types of human skin and hair follicles, and even produced structurally recognizable hair shaft, raising the possibility that they may eventually enable hair regeneration in people. Dr. Xu and his team, which includes researchers from Penn's Departments of Dermatology and Biology, as well as the New Jersey Institute of Technology, started with human skin cells called dermal fibroblasts. By adding three genes, they converted those cells into induced pluripotent stem cells (iPSCs), which have the capability to differentiate into any cell types in the body. They then converted the iPS cells into epithelial stem cells, normally found at the bulge of hair follicles. Starting with procedures other research teams had previously worked out to convert iPSCs into keratinocytes, Dr. Xu's team demonstrated that by carefully controlling the timing of the growth factors the cells received, they could force the iPSCs to generate large numbers of epithelial stem cells. In the Xu study, the team's protocol succeeded in turning over 25% of the iPSCs into epithelial stem cells in 18 days.

GWAS Study Identifies 11 New Genetic Associations for Asthma-with-Hay Fever

23andMe, a California-based personal genetics company, has participated in the first-ever genome-wide association study (GWAS) of the combined asthma-with-hay fever phenotype. Led by researchers at the QIMR Berghofer Medical Research Institute in Australia, the study identified 11 independent genetic markers associated with the development of asthma-with-hay fever, including two associations reaching a level of significance with allergic disease for the first time. Through these findings, 23andMe aims to substantially improve the ability to detect genetic risk factors shared between both diseases. Previous research has shown that both asthma and hay fever share 50-90 percent of their genetic susceptibility and 20-50 percent of their environmental susceptibility. 23andMe has collected information on both conditions through its asthma symptoms survey, and, in this analysis, used data contributed by 15,072 of its customers. Data was also collected from three additional studies conducted in Australia and the United Kingdom, with cases defined as persons who reported a physician diagnosis of asthma and also hay fever (total N=6,685). This group was compared to a control group of individuals who reported neither a diagnosis of asthma or hay fever (total N=14,091). “While previous analyses provided evidence of a stronger genetic association of this combined phenotype, there has not been a genome-wide association study exploring the connection in further detail,” said David Hinds, Ph.D., study author and 23andMe principal scientist in statistical genetics.