Harunobu Kagawa 博士によるセミナーを開催いたします。皆様のご来聴を心より歓迎いたします。
(Seminar in English)

https://www.bioreg.kyushu-u.ac.jp/mib/topics/seminar/r20261130_j.html

第861回　生医研セミナー/ The 861th MIB Seminar

日時：2026年11月30日（月）10:30–11:30 / 10:30–11:30, Nov. 30 (Mon), 2026
 

場所：病院キャンパス 総合研究棟 2階 ITルーム / IT Room, 2F, Biomedical Research Station, Hospital Campus
 

演者：Harunobu Kagawa, PhD
 

所属：Group Leader　CR2TI-U1064 The Center for Research in Transplantation and Translational Immunology, France
 

タイトル：Generation of a Human Hypoblast Model to Investigate Cell Fate Specification and Self-Organization
 

要旨：
The hypoblast plays essential roles during early human embryogenesis by regulating epiblast development and contributing to anterior–posterior axis formation through the emergence of the anterior visceral endoderm (AVE). However, the molecular mechanisms controlling hypoblast specification and the acquisition of anterior identity remain poorly understood due to the limited accessibility of human embryos.
Here, we establish an in vitro human embryonic stem cell (hESC)-based model to investigate hypoblast differentiation and early cell fate specification. Using defined culture conditions, naïve hESCs efficiently differentiate into hypoblast-like cells expressing canonical markers including GATA4, SOX17, and PDGFRA. Time-course and molecular analyses reveal the progressive acquisition of hypoblast identity and the emergence of distinct cell populations, suggesting previously unappreciated heterogeneity during differentiation.
To investigate the signalling requirements for anterior hypoblast specification, we examined the effects of ACTIVIN and FGF/ERK signalling during differentiation. We found that sustained ACTIVIN signalling is required for the induction and maintenance of an AVE-like identity, while inhibition of MEK signalling abolishes the expression of anterior markers. These findings indicate that ACTIVIN and MEK signalling cooperate to promote the acquisition of AVE-like fate in differentiating hypoblast cells.
Together, these results establish a robust and scalable platform to investigate human hypoblast development and provide new insights into the signalling mechanisms regulating AVE-like specification. Ongoing studies using micropatterned culture systems will determine how signalling dynamics and self-organization coordinate the emergence of anterior identity during early human development.

参考文献：

1. Kagawa H, Javali A, Heidari Khoei H, et al. Human blastoids model blastocyst development and implantation. Nature. 2022;601:600-605. doi: 10.1038/s41586-021-04267-8.
2. Heidari Khoei H, Javali A, Kagawa H, et al. Generating human blastoids modeling blastocyst-stage embryos and implantation. Nature Protocols. 2023;18:1584-1620. doi: 10.1038/s41596-023-00802-1.
3. Iyer DP, Heidari Khoei H, van der Weijden VA, Kagawa H, et al. mTOR activity paces human blastocyst stage developmental progression. Cell. 2024;187:6566-6583.e22. doi: 10.1016/j.cell.2024.08.048.

連絡先：

落合 博
生体防御医学研究所　遺伝子発現動態学分野
ochiai.hiroshi.403[＠]m.kyushu-u.ac.jp
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092-642-6882

Hiroshi Ochiai
Division of Gene Expression Dynamics, Medical Institute of Bioregulation
E-mail: ochiai.hiroshi.403[＠]m.kyushu-u.ac.jp
(Please remove the square brackets and replace them with the '@' symbol.)
Tel: 092-642-6882