科学者たち、ヒト発生における一時停止ボタンの可能性を発見(Scientists discover potential pause button in human development)

2024-09-26 マックス・プランク研究所

<関連情報>

• https://www.mpg.de/23507550/0926-moge-scientists-discover-pause-button-in-human-development-151795-x
• https://www.cell.com/cell/fulltext/S0092-8674(24)00977-2

mTOR活性がヒト胚盤胞の発生進行を遅らせる mTOR activity paces human blastocyst stage developmental progression

Dhanur P. Iyer∙ Heidar Heidari Khoei∙ Vera A. van der Weijden∙ … ∙ Kathy K. Niakan∙ Nicolas Rivron∙ Aydan Bulut-Karslioğlu
Cell  Published:September 26, 2024
DOI:https://doi.org/10.1016/j.cell.2024.08.048

Graphical abstract

Highlights

•Human pluripotent cells are capable of entering a reversible dormant state
•Human blastoids under mTOR inhibition show a diapause-like response
•Dormant human blastoids show altered developmental progression and attachment
•Species-specific metabolic profiles of mouse and human cells can be seen in dormancy

Summary

Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here, we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies.