High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures.
High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures.
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DOI：
10.7554/elife.59445
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发表时间：
2020-11-18
期刊：
影响因子：
7.7
通讯作者：
Solnica-Krezel L
中科院分区：
文献类型：
--
作者：
Minn KT;Fu YC;He S;Dietmann S;George SC;Anastasio MA;Morris SA;Solnica-Krezel L
在哺乳动物原肠胚形成期间，胚层出现并形成身体平面，而胚外层维持胚胎。在细胞外基质微盘上与BMP 4一起培养的人胚胎干细胞可重复地分化为类胃细胞，表达放射状排列的胚层和胚外细胞的标志物。使用单细胞RNA测序和跨物种的比较与小鼠，食蟹猴原肠胚，和植入后的人类胚胎，我们发现，gastruloid包含细胞转录相似的外胚层，外胚层，中胚层，内胚层，原始生殖细胞，滋养外胚层，羊膜。在胃状体解离后，重新附着在微圆盘上的单细胞是能动的，并且与相同的但与不同的细胞类型分离的细胞聚集。外胚层细胞与内胚层和胚外胚层分离，但与中胚层细胞混合。我们的工作表明，gastruloid系统模型灵长类动物特有的胚胎发育特征，gastruloid细胞表现出进化保守的分选行为。这项工作产生了一个资源的转录组的人胚外和胚胎胚层分化的定型安排。
During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.