美国宾夕法尼亚大学Nicolas Plachta等研究人员合作发现，人类胚胎活体成像揭示囊胚扩张和活检过程中的核DNA脱落现象。相关论文于2023年7月5日在线发表在《细胞》杂志上。

研究人员表示，恰当的植入前发育对于组建能够植入的囊胚至关重要。活体成像已经发现了驱动小鼠胚胎早期发育的主要事件。然而，对人类的研究却因遗传操作的限制和缺乏成像方法而受到限制。

研究人员克服了这一障碍，将荧光染料与活体成像相结合，揭示了人类胚胎中染色体分离、致密化、极化、囊胚形成和孵化的动态过程。研究人员还显示，囊胚的扩张对滋养层细胞有机械性的限制，导致核出芽和DNA脱落到细胞质中。此外，核周围角蛋白水平较低的细胞更容易发生DNA脱落。此外，应用滋养层活检——一种临床上用于基因测试的机械程序，会增加DNA的脱落。

因此，这项工作揭示了与小鼠不同的人类发育过程，并表明人类胚胎的非整倍体可能不仅源于有丝分裂过程中的染色体分离错误，而且也源于核DNA的脱落。

附：英文原文

Title: Human embryo live imaging reveals nuclear DNA shedding during blastocyst expansion and biopsy

Author: Ana Domingo-Muelas, Robin M. Skory, Adam A. Moverley, Goli Ardestani, Oz Pomp, Carmen Rubio, Piotr Tetlak, Blake Hernandez, Eric A. Rhon-Calderon, Luis Navarro-Sánchez, Carmen M. García-Pascual, Stephanie Bissiere, Marisa S. Bartolomei, Denny Sakkas, Carlos Simón, Nicolas Plachta

Issue&Volume: 2023-07-05

Abstract: Proper preimplantation development is essential to assemble a blastocyst capable ofimplantation. Live imaging has uncovered major events driving early development inmouse embryos; yet, studies in humans have been limited by restrictions on geneticmanipulation and lack of imaging approaches. We have overcome this barrier by combiningfluorescent dyes with live imaging to reveal the dynamics of chromosome segregation,compaction, polarization, blastocyst formation, and hatching in the human embryo.We also show that blastocyst expansion mechanically constrains trophectoderm cells,causing nuclear budding and DNA shedding into the cytoplasm. Furthermore, cells withlower perinuclear keratin levels are more prone to undergo DNA loss. Moreover, applyingtrophectoderm biopsy, a mechanical procedure performed clinically for genetic testing,increases DNA shedding. Thus, our work reveals distinct processes underlying humandevelopment compared with mouse and suggests that aneuploidies in human embryos maynot only originate from chromosome segregation errors during mitosis but also fromnuclear DNA shedding.

DOI: 10.1016/j.cell.2023.06.003

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00643-8