Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs.
Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs.
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DOI：
10.1016/j.cell.2022.07.028
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发表时间：
2022-09-01
期刊：
影响因子：
64.5
通讯作者：
Flannel, Jacob H.
中科院分区：
文献类型：
--
作者：
Tarazi, Shadi;Aguilera-Castrejon, Alejandro;Joubran, Carine;Ghanem, Nadir;Ashouokhi, Shand;Roncato, Francesco;Wildschutz, Emilie;Haddad, Montaser;Oldak, Bernardo;Gomez-Cesar, Elidet;Livnat, Nir;Viukov, Sergey;Lokshtanov, Dmitry;Naveh-Tassa, Segev;Rose, Max;Hanna, Suhair;Raanan, Calanit;Brenner, Ori;Kedmi, Merav;Keren-Shaul, Hadas;Lapidot, Tsvee;Maza, Itay;Novershtern, Noa;Flannel, Jacob H.
体外培养的干细胞具有不同的发育能力，显微注射到植入前的哺乳动物胚胎中后，可以促进胚胎或胚外组织。然而，培养的干细胞是否能够独立地产生具有胚胎和胚外区室的整个原肠胚样结构仍然未知。在这里，我们采用了最近建立的天然胚胎长时间子宫外生长的平台，以生成小鼠原肠胚形成后合成全胚胎模型（sEmbryos），其中包括胚胎和胚外区室，仅从幼稚ESC开始。这是通过共聚集未转导的ESC来实现的，其中幼稚ESC瞬时表达Cdx2或Gata4以分别促进它们向滋养外胚层和原始内胚层谱系的引发。sEmbryos充分完成原肠胚形成，通过关键发育里程碑前进，并在类似于E8.5阶段小鼠胚胎的复杂胚外隔室中发育器官祖细胞。我们的研究结果强调了幼稚多能细胞自我组织和功能重建的可塑性潜力，并模拟了整个哺乳动物胚胎的原肠胚形成。高级合成胚胎（sEmbryos）在子宫外设置中从ESC自组装幼稚ESC在sEmbryos中产生所有胚胎和胚外区室原肠胚形成后干细胞衍生的sEmbryos发育器官特异性祖细胞胚外区室在原肠胚形成后完整sEmbryos发育的原肠胚形成后阶段，具有器官祖细胞和复杂的胚外祖细胞。胚胎区室完全由组装的幼稚小鼠胚胎干细胞在子宫外获得。
In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic 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 extraembryonic 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 extraembryonic compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, with naive ESCs transiently expressing Cdx2 or Gata4 to promote their priming toward trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naive pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation. Advanced synthetic embryos (sEmbryos) self-assembled from ESCs in an ex utero setup Naive ESCs give rise to all embryonic and extraembryonic compartments in sEmbryos Post-gastrulation stem cell derived sEmbryos develop organ-specific progenitors Extraembryonic compartments adequately develop in post-gastrulation whole sEmbryos Post-gastrulation stages of development with organ progenitors and complex extra-embryonic compartments are achieved ex utero entirely from assembled naive mouse embryonic stem cells.
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影响因子：
32.4
作者：
Iturri L;Freyer L;Biton A;Dardenne P;Lallemand Y;Gomez Perdiguero E
通讯作者：
Gomez Perdiguero E
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Aguilera-Castrejon, Alejandro;Oldak, Bernardo;Hanna, Jacob H.
通讯作者：
Hanna, Jacob H.
影响因子：
11.8
作者：
Amadei G;Lau KYC;De Jonghe J;Gantner CW;Sozen B;Chan C;Zhu M;Kyprianou C;Hollfelder F;Zernicka-Goetz M
通讯作者：
Zernicka-Goetz M
影响因子：
64.8
作者：
Kagawa H;Javali A;Khoei HH;Sommer TM;Sestini G;Novatchkova M;Scholte Op Reimer Y;Castel G;Bruneau A;Maenhoudt N;Lammers J;Loubersac S;Freour T;Vankelecom H;David L;Rivron N
通讯作者：
Rivron N