1: Tumour resistance in induced pluripotent stem cells derived from naked mole-rats.
Science of the Month - July 2016
Nature Communications
2016; 7:11471.doi: 10.1038/ncomms11471.
Shingo Miyawaki, Yoshimi Kawamura, Yuki Oiwa, Atsushi Shimizu, Tsuyoshi Hachiya,Hidemasa Bono, Ikuko Koya, Yohei Okada, Tokuhiro Kimura, Yoshihiro Tsuchiya, Sadafumi Suzuki, Nobuyuki Onishi, Naoko Kuzumaki, Yumi Matsuzaki, Minoru Narita, Eiji Ikeda,Kazuo Okanoya, Ken-ichiro Seino, Hideyuki Saya, Hideyuki Okano, et al.
A research group led by Shingo Miyawaki, Kyoko Miura (formerly of the Department of Physiology, currently at Hokkaido University), and Professor Hideyuki Okano (Department of Physiology) has succeeded for the first time in the world in creating iPS cells from the naked mole-rat, a rodent with a long lifespan of about 30 years and high resistance to cancer, and has now published their paper in the journal *Nature Communications*. While iPS cells from other animals such as mice and humans have the problem of forming tumors (teratomas) if undifferentiated cells are mixed in during transplantation, iPS cells created from naked mole-rats did not form tumors even when transplanted in an undifferentiated state. Analysis of the cause revealed that naked mole-rat iPS cells do not form tumors due to the activation of the tumor suppressor gene ARF and the functional loss of the oncogene ERAS. Furthermore, it was found that activating ARF in mouse iPS cells strongly suppresses tumor formation. Applying these findings may lead to the creation of safer human iPS cells and is expected to contribute to human health, longevity, and cancer prevention in the future.
(Shingo Miyawaki, Class of 2000, Department of Epigenome Dynamics, Institute for Advanced Enzyme Research, Tokushima University)
2: Transsynaptic Modulation of Kainate Receptor Functions by C1q-like Proteins
Neuron.
Keiko Matsuda, Timotheus Budisantoso, Nikolaos Mitakidis, Yuki Sugaya, Eriko Miura, Wataru Kakegawa, Miwako Yamasaki,Kohtarou Konno, Motokazu Uchigashima, Manabu Abe, Izumi Watanabe, Masanobu Kano, Masahiko Watanabe, Kenji Sakimura,A. Radu Aricescu, Michisuke Yuzaki
In our brains, countless nerve cells connect via synapses to form neural networks. Glutamate is released from the presynaptic terminal of a nerve cell and binds to glutamate receptors on the postsynaptic terminal of the next nerve cell, thereby transmitting excitement. Among the subtypes of glutamate receptors, kainate receptors are particularly abundant at specific synapses in the hippocampus, a brain region important for memory and learning. With their slow transmission speed, they play an essential role in integrating the neural network activity of the hippocampus. In pathological conditions, they also cause epileptic seizures. However, how kainate receptors localize to specific synapses was a complete mystery. We discovered a new mechanism whereby the presynaptic terminal secretes proteins called C1ql2 and C1ql3 to gather kainate receptors at specific postsynaptic sites. In the hippocampus of mice lacking C1ql2 and C1ql3, we found that kainate receptors were not incorporated into synapses, making seizures less likely to occur even when a stimulus that induces epilepsy was applied. The results of this research are expected to be useful for elucidating normal brain function and developing treatments for epilepsy.
(Michisuke Yuzaki, Class of 1964, and Keiko Matsuda, Department of Physiology)
Other Published Papers
1: Improved Survival of Patients with Pulmonary Arterial Hypertension with BMPR2 Mutations in the Last Decade.
American Journal of Respiratory and Critical Care Medicine,
Vol. 193, No. 11 (2016), pp. 1310-1314.
Sarasa Isobe, Masaharu Kataoka, Yuki Aimi, Shinobu Gamou, Toru Satoh, and Keiichi Fukuda
2: Development and maintenance of intestinal regulatory T cells
NATURE REVIEWS IMMUNOLOGY,
16 (5):295-309; 10.1038/nri.2016.36 MAY 2016
Tanoue, Takeshi; Atarashi, Koji; Honda, Kenya