Delay of human early development via in vitro diapause-猫眼课题宝

DOI：

10.1101/2023.05.29.541316

发表时间：

2023-05

期刊：

bioRxiv

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Dhanur P. Iyer;V. V. D. Weijden-V.;Heidar Heidari Khoei;A. McCarthy;Teresa Rayon;Claire S. Simon;I. Dunkel;Sissy E. Wamaitha;K. Elder;Phil Snell;L. Christie;Edda G. Schulz;K. Niakan;N. Rivron;Aydan Bulut-Karslioğlu

许多哺乳动物可以通过在囊胚期暂停胚胎发育来控制妊娠和分娩的时间。目前尚不清楚暂停发育的能力是否在哺乳动物中普遍保留，尤其是在人类中。在小鼠中，生长调节mTOR通路的活性调控发育暂停(1)。在这里，我们展示了一种通过mTOR抑制延缓人类发育进程的阶段特异性能力。在这种情况下，人类囊胚和多能干细胞在naïve和naïve-like状态，但不是启动状态，可以被诱导进入休眠状态，这在功能和分子水平上是可逆的。小鼠和人类naïve细胞对mTORi的纵向反应的比较分析揭示了每个物种不同的时间动态和休眠代谢需求。小鼠和人类囊胚显示出相似的组织特异性mTOR通路活性模式，这表明mTOR通路可能是两个物种囊胚发育和时间的保守调节因子。我们的研究结果表明，人类胚胎的发育时间可能是可控的，这对生殖治疗具有重要意义。

Many mammals can control the timing of gestation and birth by pausing embryonic development at the blastocyst stage. It is unknown whether the capacity to pause development is conserved, in general across mammals, and more specifically in humans. Activity of the growth regulating mTOR pathway governs developmental pausing in the mouse (1). Here we show a stage-specific capacity to delay the progression of human development via mTOR inhibition. In this context, human blastoids and pluripotent stem cells in naïve and naïve-like, but not primed, states can be induced to enter a dormant state, which is reversible at the functional and molecular level. Comparative analysis of mouse and human naïve cells’ longitudinal response to mTORi revealed distinct temporal dynamics and metabolic requirements of dormancy in each species. Mouse and human blastocysts show similar tissue-specific patterns of mTOR pathway activity, suggesting that the mTOR pathway may be a conserved regulator of blastocyst development and timing in both species. Our results raise the possibility that the developmental timing of the human embryo may be controllable, with implications for reproductive therapies.

Delay of human early development via in vitro diapause

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