The 861st MIB Seminar
(Joint Usage/Research Center for the Multi-stratified Host Defense System)
Title
Generation of a Human Hypoblast Model to Investigate Cell Fate Specification and Self-Organization
Speaker
Harunobu Kagawa, PhD
Group Leader
CR2TI-U1064 The Center for Research in Transplantation and Translational Immunology, France
Group Leader
CR2TI-U1064 The Center for Research in Transplantation and Translational Immunology, France
Date
Nov. 30 (Mon), 2026
10:30–11:30
10:30–11:30
Venue
IT Room, 2F, Biomedical Research Station, Hospital Campus
(Building No. 35 on the [Campus Map])
(Building No. 35 on the [Campus Map])
Abstract
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.
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.
References
- 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.
- 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.
- 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.
Contact
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
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