近日，德国马克斯·普朗克分子遗传学研究所Aydan Bulut-Karsliolu等研究人员合作发现，mTOR活性加快人类囊胚阶段的发展进程。该研究于2024年9月26日在线发表于国际一流学术期刊《细胞》。

研究人员发现，降低mTOR信号通路的活性会诱导人类多能干细胞（hPSC）和囊胚进入一个限制增殖、发育进程和附着于子宫内膜细胞的休眠状态。这些体外实验表明，与其他物种类似，人体细胞在囊胚阶段进入休眠的能力是活跃的，并且在功能和分子水平上都是可逆的。调节人类囊胚发育的节奏可能对生殖治疗具有潜在影响。

据了解，许多哺乳动物能够在囊胚阶段减缓其发育，从而在时间上将受孕与分娩分离。在小鼠中，这种休眠状态是通过降低生长调节mTOR信号通路的活性来实现的。目前尚不清楚这种能力是否在一般哺乳动物中得到保留，尤其是在人体中。

附：英文原文

Title: mTOR activity paces human blastocyst stage developmental progression

Author: Dhanur P. Iyer, Heidar Heidari Khoei, Vera A. van der Weijden, Harunobu Kagawa, Saurabh J. Pradhan, Maria Novatchkova, Afshan McCarthy, Teresa Rayon, Claire S. Simon, Ilona Dunkel, Sissy E. Wamaitha, Kay Elder, Phil Snell, Leila Christie, Edda G. Schulz, Kathy K. Niakan, Nicolas Rivron, Aydan Bulut-Karsliolu

Issue&Volume: 2024-09-26

Abstract: 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.

DOI: 10.1016/j.cell.2024.08.048

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00977-2