Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids.
Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids.
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DOI：
10.1016/j.stemcr.2021.03.031
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发表时间：
2021-05-11
影响因子：
5.9
通讯作者：
Solnica-Krezel L
中科院分区：
文献类型：
--
作者：
Minn KT;Dietmann S;Waye SE;Morris SA;Solnica-Krezel L
在具有BMP 4的2D微模式中培养的人胚胎干细胞分化成放射状排列的胚层和胚外细胞。单细胞转录组证明了在卡内基7期人原肠胚中与其体内对应物在转录上相似的细胞类型的产生。时程分析表明顺序分化，其中的外胚层之间的前瞻性外胚层在中心和细胞开始分化向胚胎外的命运在边缘的12小时出现。胚外和中内胚层前体细胞在24 h时从上胚层产生，而新生的中胚层、内胚层和原始生殖细胞样细胞在44 h时形成。编码信号传导组分的转录物的动态变化支持BMP、WNT和Nodal层次结构，这些层次结构是哺乳动物中保守的胚层特化的基础，并且FGF和HIPPO途径在整个分化过程中是活跃的。这项工作还提供了一个资源，用于挖掘在定型的2D gastruloid模型中表达的基因和途径，这些模型与其他物种共同或独特于人类原肠胚形成。hESC 2D类原肠胚形成三个胚层、胚外细胞和PGC样细胞scRNA-seq显示2D类原肠胚和CS 7人原肠胚具有相似的细胞类型上胚层、外胚层、ExE、中胚层、内胚层和PGC细胞的顺序出现保存的BMP、WNT和作为胚层特化基础的结节等级在这篇文章中，Solnica-Krezel及其同事分析了BMP 4诱导的hESC 2D微图案化类胃窦的细胞转录组，以显示它们具有与Carnegie 7期人类原肠胚相似的细胞组成。他们证明连续出现的上胚层和外胚层，其次是胚外和中内胚层前体，最后是中胚层，内胚层和原始生殖细胞。它们为挖掘人类原肠胚形成的基因提供了资源。
Human embryonic stem cells cultured in 2D micropatterns with BMP4 differentiate into a radial arrangement of germ layers and extraembryonic cells. Single-cell transcriptomes demonstrate generation of cell types transcriptionally similar to their in vivo counterparts in Carnegie stage 7 human gastrula. Time-course analyses indicate sequential differentiation, where the epiblast arises by 12 h between the prospective ectoderm in the center and the cells initiating differentiation toward extraembryonic fates at the edge. Extraembryonic and mesendoderm precursors arise from the epiblast by 24 h, while nascent mesoderm, endoderm, and primordial germ cell-like cells form by 44 h. Dynamic changes in transcripts encoding signaling components support a BMP, WNT, and Nodal hierarchy underlying germ-layer specification conserved across mammals, and FGF and HIPPO pathways being active throughout differentiation. This work also provides a resource for mining genes and pathways expressed in a stereotyped 2D gastruloid model, common with other species or unique to human gastrulation. hESCs 2D gastruloids form three germ layers, extraembryonic and PGC-like cells scRNA-seq shows that 2D gastruloids and CS7 human gastrula have similar cell types Sequential emergence of epiblast, ectoderm, ExE, mesoderm, endoderm, and PGC cells Conserved BMP, WNT, and Nodal hierarchy underlying germ layer specification In this article, Solnica-Krezel and colleagues analyze cellular transcriptomes of BMP4-induced hESC 2D micropatterned gastruloids to show they have cellular composition similar to that of Carnegie stage 7 human gastrula. They demonstrate successive emergence of epiblast and ectoderm, followed by extraembryonic and mesendoderm precursors, and finally mesoderm, endoderm, and primordial germ cells. They provide a resource for mining genes underlying human gastrulation.
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