Human blastoids model blastocyst development and implantation.
Human blastoids model blastocyst development and implantation.
复制标题
DOI：
10.1038/s41586-021-04267-8
复制
发表时间：
2022-01
期刊：
影响因子：
64.8
通讯作者：
Rivron N
中科院分区：
文献类型：
--
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
受精一周后，人类胚胎植入子宫。该事件需要胚胎形成囊胚，囊胚由围绕容纳胚胎的空腔的球体组成。干细胞可以形成囊胚模型，我们称之为胚泡。在这里，我们展示了在 PXGL 培养基中培养并三重抑制 Hippo、TGF-β 和 ERK 途径的初始人类多能干细胞，根据囊胚发育的顺序和时间，有效（效率超过 70%）形成胚泡，产生三个创始谱系（超过 97% 的滋养外胚层、外胚层和原始内胚层）的囊胚阶段类似物。胚泡自发形成第一轴，我们观察到外胚层诱导极滋养外胚层的局部成熟，从而赋予胚泡定向附着于激素刺激的子宫内膜细胞的能力，就像在植入期间一样。因此，我们认为这样的人类类胚体是研究人类植入和发育的忠实、可扩展且合乎道德的模型。源自初始 PXGL 培养的人类多能干细胞的胚泡，其中 Hippo、TGF-β 和 ERK 途径受到抑制，密切再现了囊胚发育的各个方面，形成类似于囊胚阶段细胞的细胞，从而为植入和发育研究提供了模型系统。
One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid. Here we show that naive human pluripotent stem cells cultured in PXGL medium and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development. Blastoids derived from naive PXGL-cultured human pluripotent stem cells in which Hippo, TGF-β and ERK pathways are inhibited closely recapitulate aspects of blastocyst development, form cells resembling blastocyst-stage cells and thus provide a model system for implantation and development studies.
登录
查看更多内容
影响因子：
5.9
作者：
Guo G;von Meyenn F;Santos F;Chen Y;Reik W;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
33.5
作者：
Fan Y;Min Z;Alsolami S;Ma Z;Zhang E;Chen W;Zhong K;Pei W;Kang X;Zhang P;Wang Y;Zhang Y;Zhan L;Zhu H;An C;Li R;Qiao J;Tan T;Li M;Yu Y
通讯作者：
Yu Y
影响因子：
4.6
作者：
Boretto, Matteo;Cox, Benoit;Vankelecom, Hugo
通讯作者：
Vankelecom, Hugo
影响因子：
8.8
作者：
Messmer, Tobias;von Meyenn, Ferdinand;Reik, Wolf
通讯作者：
Reik, Wolf
影响因子：
56.9
作者：
Dumortier, Julien G.;Le Verge-Serandour, Mathieu;Maitre, Jean-Leon
通讯作者：
Maitre, Jean-Leon