以色列魏茨曼科学研究所Jacob H. Hanna团队从初始ES细胞中获得完整的人类植入后第14天胚胎模型。这一研究成果于2023年9月6日在线发表在国际学术期刊《自然》上。

研究人员表示，由于与植入后宫内发育相关的伦理和技术挑战，研究人类植入后发育的能力仍然有限。目前仍缺乏胚胎样模型，其能在空间上组织胚胎植入后人类受孕体的所有胚胎和胚外组织（即胚盘、二胚层胚盘、卵黄囊和绒毛膜囊、周围滋养细胞）的形态发生。小鼠初始胚胎干细胞（ESC）最近被证明能产生胚胎干细胞和胚外干细胞，并能自我组装成具有空间组织形态发生（SEM）的原肠运动后基于干细胞的小鼠胚胎模型。

研究人员将这些发现扩展到人类，同时只使用未经基因修饰的人类初始干细胞（在HENSM条件下）。这种完全整合的人类SEM重现了植入后人类胚胎几乎所有已知谱系和区室的组织，包括上胚层、下胚层、胚外中胚层和围绕后层的滋养层。这些人类完整的扫描电子显微镜显示了与受精后13-14天（dpf）（卡内基阶段6a）胚胎着床后阶段的主要特征相似的发育生长动态。这包括胚盘和二胚层胚盘的形成、上胚层管腔的形成、极化羊膜的形成、前后对称性的打破、PGC的特化、带有内脏和顶叶内胚层的极化卵黄囊、胚外中胚层的扩张（它定义了一个绒毛腔和一个连接柄）、滋养层周围的小室（显示了合子和裂隙的形成）。

这种扫描电子显微镜平台可以对以前无法获取的人类胚胎植入后早期直至围原肠运动的窗口进行实验研究。

附：英文原文

Title: Complete human day 14 post-implantation embryo models from nave ES cells

Author: Oldak, Bernardo, Wildschutz, Emilie, Bondarenko, Vladyslav, Comar, Mehmet-Yunus, Zhao, Cheng, Aguilera-Castrejon, Alejandro, Tarazi, Shadi, Viukov, Sergey, Pham, Thi Xuan Ai, Ashouokhi, Shahd, Lokshtanov, Dmitry, Roncato, Francesco, Ariel, Eitan, Rose, Max, Livnat, Nir, Shani, Tom, Joubran, Carine, Cohen, Roni, Addadi, Yoseph, Chemla, Muriel, Kedmi, Merav, Keren-Shaul, Hadas, Pasque, Vincent, Petropoulos, Sophie, Lanner, Fredrik, Novershtern, Noa, Hanna, Jacob H.

Issue&Volume: 2023-09-06

Abstract: The ability to study human post-implantation development remains limited due to ethical and technical challenges associated with intrauterine development after implantation1. Embryo-like models with spatially organized morphogenesis of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (i.e., embryonic disk, bilaminar disk, yolk- and chorionic sacs, surrounding trophoblasts) remain lacking2. Mouse naïve embryonic stem cells (ESCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse Structured Stem cell-based Embryo Models with spatially organized morphogenesis (SEMs)3. Here, we extend these findings to humans, while using only genetically unmodified human naïve ESCs (in HENSM conditions)4. Such human fully integrated SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf) (Carnegie stage 6a). This includes embryonic disk and bilaminar disk formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, PGC specification, polarized yolk sac with visceral and parietal endoderm, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, a trophoblast surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform may enable the experimental interrogation of previously inaccessible windows of human early post-implantation up to peri-gastrulation development.

DOI: 10.1038/s41586-023-06604-5

Source: https://www.nature.com/articles/s41586-023-06604-5