1: Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors.
Science of the Month - March 2018
Genes & Dev
Chai M, Sanosaka T, Okuno H, Zhou Z, Koya I, Banno S, Andoh-Noda T, Tabata Y, Shimamura R, Hayashi T, Ebisawa M, Sasagawa Y, Nikaido I, Okano H*, and Kohyama J*. (* Corresponding Authors)
The establishment of human iPS cell technology has made it possible to analyze diseases using patient-derived cells. Our research group has been conducting analyses focusing on epigenetic gene expression regulatory mechanisms, and we proceeded with an analysis focusing on CHARGE syndrome, as mutations or deletions in factors that control epigenetics are found in pediatric diseases. CHARGE syndrome is a congenital disorder primarily characterized by dual sensory impairment of vision and hearing, and in 2004, it was reported to be associated with spontaneous mutations in the CHD7 gene. Although CHD7 is known as a chromatin remodeling factor, its detailed functions and its involvement in the pathology of CHARGE syndrome were not clear. Therefore, we used next-generation sequencing to search for target regions of CHD7 and found that CHD7 binds to central nervous system-specific enhancer regions and maintains their activity. Furthermore, by using shRNA against CHD7 and patient-derived cells, we revealed that CHD7 maintains the properties of neural progenitor cells. We also found that the disruption of this function significantly impairs the ability to differentiate into neurons, causing neural progenitor cells to transdifferentiate into neural crest-like cells. We also identified genes such as SOX21 and BRN2 as causes of these abnormalities and found that these factors could rescue the abnormalities in neural progenitor cells caused by CHD7 defects. Similar approaches can be applied to other congenital disorders, and it is hoped that this will lead to the establishment of treatments for these diseases.
(Jun Kohyama, Department of Physiology, 81st graduating class)
2: Japan strengthens regenerative medicine oversight.
On November 25, 2014, in line with the government's policy to promote regenerative medicine, the Act on the Safety of Regenerative Medicine and the revised Pharmaceutical Affairs Act (now the PMD Act) were enacted in Japan, leading to significant changes in the regulatory landscape for regenerative medicine. In this Cell Stem Cell paper, Professor Hideyuki Okano of the School of Medicine's Department of Physiology and the Keio University Global Research Institute (KGRI), and Project Professor Douglas Sipp analyze the current state of regenerative medicine regulation in Japan as follows. Under the Act on the Safety of Regenerative Medicine, plans for providing regenerative medicine (for both medical treatment and research) are now classified into Class I, Class II, and Class III based on their level of risk and novelty. This is because one of the aims of this act was to establish an approval system for regenerative medicine practices, which were previously unregulated. Looking at the number of cases approved by Special Certified Committees for Regenerative Medicine or Certified Committees for Regenerative Medicine, Class III cases are overwhelmingly predominant (approx. 97%). Out of a total of 3,541 cases, Class III medical practices, which were previously unregulated treatments, account for as many as 3,486 cases (as of August 31, 2017), making quality control a significant issue. Meanwhile, the enforcement of the act has led to the arrest and conviction of a physician who performed unnotified regenerative medicine procedures using umbilical cord blood. In response, the government is moving toward revising the act to increase transparency in its implementation. The legal framework for regenerative medicine is in its fourth year since enforcement and can be said to be still in a developmental stage. This paper also analyzes the situation in other countries that have been spurred by Japan's legislation, such as the amendments to regenerative medicine-related laws in the United States under the 21st Century Cures Act.
(Hideyuki Okano, Department of Physiology, 62nd graduating class)
Other Publications
1: gamma delta TCR recruits the Syk/PI3K axis to drive proinflammatory differentiation program
JOURNAL OF CLINICAL INVESTIGATION
128 (1):415-426; 10.1172/JCI95837 JAN 2 2018
Muro Ryunosuke, Nitta Takeshi, Nakano Kenta, Okamura Tadashi, Takayanagi Hiroshi, Suzuki Harumi