Yoshihiro Yamanaka

Yoshihiro Yamanaka

Researcher (Alev-G)

Program-Specific Researcher
Research Field
Developmental Biology

Research Overview

In vitro reconstitution and comparative analysis of somitogenesis and musculoskeletal development

Somitogenesis is a major developmental event during which the axial skeleton of the embryo is formed and patterned. Our knowledge of this important developmental process is largely based on model organisms such as mice, chicken or zebrafish, while our understanding of human somitogenesis remains limited. I am interested in how somites and the musculoskeletal system form and how they are shaped in a robust and controlled manner during early development. We recently established an embryonic development-inspired induced pluripotent stem cell (iPSC)-based method for the stepwise induction and differentiation of presomitic mesoderm (PSM), and utilized it for the in vitro recapitulation of the human segmentation clock (Matsuda, Yamanaka et al., Nature 2020). We initially proved that our induced PSM cells can give rise to somitic mesoderm and its two main derivatives, sclerotome and dermomyotome, which further differentiate into bone and cartilage or skeletal muscle and dermis, respectively. We then determined that the period of the human segmentation clock, a molecular oscillator that is believed to control somite formation, is around 5 hours in our in vitro-derived human PSM cells. We also showed that the period of the mouse segmentation clock is 2-3 hours in murine EpiSC-derived PSM cells. In addition, in vitro induced human PSM showed traveling wave-like oscillatory activity, which is another feature of somitogenesis. We further performed RNAseq analysis and found novel oscillating genes in mouse and human induced PSMs, with some being evolutionary conserved between both species while others are species-specific. We then applied our model system to the analysis of diseases characterized by segmentation defects of the spine. Combining patient-derived and patient-like iPSCs with our model system, we identified disease-specific features, including alterations in oscillation, synchronization or differentiation properties in in vitro induced patient PSMs and their derivatives. Building upon these promising findings, I am currently continuing to establish in the Alev Group advanced systems for the in vitro recapitulation and analysis of human and non-human somite formation and patterning. Applying our embryonic development-inspired in vitro model systems I want to understand how the segmentation clock is linked to the process of somite formation and patterning in human and other species. My overall aim is to clarify the mechanisms underlying inter-species differences during somitogenesis and musculoskeletal development.

Fig.1. Z stack movie of stained human iPSC line and Time-lapse imaging of human iPSC-reporter line cultured in 3D.


Yoshihiro Yamanaka obtained his B.S. degree in Science and Engineering in 2015 from Kwansei Gakuin University. He joined the Master of Science Program in Medical Sciences in the laboratory of Dr. Junya Toguchida at the Center for iPS Cell Research and Application (CiRA) at Kyoto University. He obtained his M.S. degree in Medical Science in 2017 and then joined the Doctoral Program in Medical Sciences at the Graduate School of Medicine in Kyoto University. He continues to work in the Alev Lab at the Institute for the Advanced Study of Human Biology (ASHBi) and obtained his Ph.D. from Kyoto University in 2020.


Scholarship (Master course) from Iwadare Scholarship Foundation (2016)
Scholarship (PhD course) from Iwadare Scholarship Foundation (2018)


Yann Pretemer, Shunsuke Kawai, Makoto Watanabe, Sanae Nagata, Megumi Nishio, Sakura Tamaki, Cantas Alev, Yoshihiro Yamanaka, Jing-Yi Xue, Zheng Wang, Kenichi Fukiage, Masako Tsukanaka, Tohru Futami, Shiro Ikegawa, Junya Toguchida. Human iPSC-derived hypertrophic chondrocytes reveal a mutation-specific unfolded protein response in chondrodysplasias. Stem Cell Reports. 2021 Mar doi: https://doi.org/10.1016/j.stemcr.2021.01.014

Mitsuhiro Matsuda, Hanako Hayashi, Jordi Garcia-Ojalvo, Kumiko Yoshioka-Kobayashi, Ryoichiro Kageyama, Yoshihiro Yamanaka, Makoto Ikeya, Junya Toguchida, Cantas Alev, Miki Ebisuya. Species-specific oscillation periods of human and mouse segmentation clocks are due to cell autonomous differences in biochemical reaction parameters. Science. 2020 Sep doi: https://doi.org/10.1126/science.aba7668

Mitsuhiro Matsuda*, Yoshihiro Yamanaka*, Maya Uemura, Mitsujiro Osawa, Megumu K. Saito, Ayako Nagahashi, Megumi Nishio, Long Guo, Shiro Ikegawa, Satoko Sakurai, Shunsuke Kihara, Thomas L. Maurissen, Michiko Nakamura, Tomoko Matsumoto, Hiroyuki Yoshitomi, Makoto Ikeya, Noriaki Kawakami, Takuya Yamamoto, Knut Woltjen, Miki Ebisuya, Junya Toguchida, Cantas Alev. Recapitulating the Human Segmentation Clock with Pluripotent Stem Cells. Nature. 2020 Apr;580(7801):124-129. https://doi.org/10.1038/s41586-020-2144-9 *equally contributing co-first author

Yoshihiro Yamanaka., Maya Uemura, Cantas Alev. Stepwise in vitro induction of human somitic mesoderm and its derivatives. Protocol Exchange. 2020 Apr doi: https://doi.org/10.21203/rs.2.22919/v1

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