近日,以色列魏茨曼科学研究所Jacob H. Hanna等研究人员合作发现,小鼠初始ESC能够在子宫外产生原肠运动后的合成胚胎。该研究于2022年8月1日在线发表于国际一流学术期刊《细胞》。
研究人员调整了最近建立的一个延长自然胚胎宫外生长的平台,从而生成小鼠原肠运动后的合成全胚胎模型(sEmbryo),同时具有胚胎和胚胎外的部分,仅仅从初始的ESC开始。这是通过共聚集ESC来实现的,其中初始的ESC瞬时表达Cdx2-和Gata4-来促进它们分别向滋养外胚层和原始内胚层谱系的启动。sEmbryo能充分完成原肠运动,通过关键的发育里程碑前进,并在复杂的胚外区间发展器官祖先,类似于E8.5期小鼠胚胎。这项研究结果突出了初始多能细胞的可塑性潜力,可以自我组织和功能重组,并对整个哺乳动物的胚胎在原肠运动之后进行建模。
据介绍,体外培养的干细胞具有不同的发育能力,在微注射到植入前的哺乳动物胚胎中后,可以为胚胎或胚胎外组织作出贡献。然而,培养的干细胞是否能独立地产生具有胚胎和胚胎外区的整个原肠样结构,仍是未知数。
附:英文原文
Title: Post-Gastrulation Synthetic Embryos Generated Ex Utero from Mouse Nave ESCs
Author: Shadi Tarazi, Alejandro Aguilera-Castrejon, Carine Joubran, Nadir Ghanem, Shahd Ashouokhi, Francesco Roncato, Emilie Wildschutz, Montaser Haddad, Bernardo Oldak, Elidet Gomez-Cesar, Nir Livnat, Sergey Viukov, Dmitry Lukshtanov, Segev Naveh-Tassa, Max Rose, Suhair Hanna, Calanit Raanan, Ori Brenner, Merav Kedmi, Hadas Keren-Shaul, Tsvee Lapidot, Itay Maza, Noa Novershtern, Jacob H. Hanna
Issue&Volume: 2022-08-01
Abstract: In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extra-embryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extra-embryonic compartments, remains unknown. Here we adapt a recently established platform for prolonged ex utero growth of natural embryos, to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extra-embryonic compartments, starting solely from nave ESCs. This was achieved by co-aggregating non-transduced ESCs, with nave ESCs transiently expressing Cdx2- and Gata4- to promote their priming towards trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extra-embryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of nave pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.
DOI: 10.1016/j.cell.2022.07.028
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00981-3
期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216