Stem Cell Chromatin Group, Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Cell. 2024 Nov 14;187(23):6566-6583.e22. doi: 10.1016/j.cell.2024.08.048. Epub 2024 Sep 26.
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.
许多哺乳动物可以通过在囊胚阶段减缓其发育来将受孕与分娩时间分离开来。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哺乳动物中普遍存在，特别是在人类中是否存在。在这里，我们表明，降低 mTOR 信号通路的活性会诱导人多能干细胞 (hPSC) 和类囊胚进入休眠状态，其增殖、发育进展和附着在内膜细胞上的能力受到限制。这些体外检测表明，与其他物种类似，在囊胚阶段人类细胞具有进入休眠的能力，并且在功能和分子水平上都是可逆的。人类囊胚发育的调节具有生殖治疗的潜在意义。
