November 28, 2017
Keio University School of Medicine
A research group led by Professor Hideyuki Okano and Assistant Professor Hironori Okuno of the Department of Physiology, Keio University School of Medicine, has elucidated, using a disease model based on patient-derived human induced pluripotent stem (iPS) cells, that the symptoms of CHARGE syndrome, a congenital disorder affecting sensory organs, are caused by a migration defect (slow cell movement speed) of neural crest cells during the embryonic stage.
For hereditary diseases where symptoms develop during the embryonic stage, it has been difficult to observe this process, and elucidating the detailed pathology has been a challenge. iPS cells, developed in 2006 by Professor Shinya Yamanaka and his team at Kyoto University, can differentiate into any type of tissue or cell. Using this technology, the research group succeeded in observing the process of embryonic cell differentiation—which was previously difficult to observe directly—by generating iPS cells from skin cells and then creating neural crest cells from the iPS cells.
CHARGE syndrome is a congenital disease that causes abnormalities in sensory organs, such as the eyes and ears, and the heart. The organs where these symptoms appear are formed by neural crest cells during the embryonic stage. It is known that CHARGE syndrome is caused by the malfunction of a gene called CHD7, but how CHD7 affects neural crest cells had not been elucidated until now.
In this study, the research group conducted a detailed comparative analysis between cells derived from CHARGE syndrome patients and those from a healthy control group. Neural crest cells derived from CHARGE syndrome patients showed characteristic differences compared to those from the control group. In particular, multifaceted analysis revealed that their cell movement speed was slower. Furthermore, genetic analysis identified a group of genes responsible for the slower movement in neural crest cells.
Through this research, it is hoped that even if it is difficult to repair the damage already formed at birth in CHARGE syndrome, identifying pathologies that can be approached to restore function in the future could lead to treatments. Additionally, this model can be applied to similarly investigate the mechanisms of various congenital diseases caused by neural crest cell defects, and it is also considered useful as part of toxicity testing (screening) for new drugs to assess their effects on the fetal neural crest. Furthermore, this model is expected to be a valuable tool for understanding the role of neural crest cells in the process of human development. The results of this research were published in the open-access journal "eLife" on November 28, 2017, at 8:00 a.m. (UK time).
For the full press release, please see below.