A single cell transcriptional portrait of embryoid body differentiation and comparison to progenitors of the developing embryo.
A single cell transcriptional portrait of embryoid body differentiation and comparison to progenitors of the developing embryo.
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DOI：
10.1016/j.scr.2018.07.022
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发表时间：
2018-08
影响因子：
1.2
通讯作者：
Cahan P
中科院分区：
文献类型：
--
作者：
Spangler A;Su EY;Craft AM;Cahan P
多能干细胞的定向分化提供了一个可用于建模发育的系统。然而，由于分化所固有的细胞异质性，早期胚胎中出现的不同细胞类型、它们的动态以及它们与祖细胞的关系一直难以破译。在这里，我们使用了批量RNA-Seq，单细胞RNA-Seq和生物信息学分析的组合来解剖小鼠胚胎干细胞定向分化为胚状体期间出现的细胞类型，并将它们与早期胚胎的空间和时间分辨的转录谱进行了比较。我们的单细胞分析的第4天胚状体揭示了三个群体，保留了相关的，但不同的多能性的签名，类似于植入前或植入后的外胚层，一个人口的推定神经外胚层，一个人口的中内胚层，和四个人口的神经祖细胞。到第6天，神经祖细胞占主导地位的胚状体，但一个小的人口的多能性细胞和前中胚层样Brachyury表达人口。通过比较第4天和第6天的群体，我们确定了候选的分化途径，转录因子和信号通路，标志着在体外相关的过渡从中期到晚期原条阶段。
Directed differentiation of pluripotent stem cells provides an accessible system to model development. However, the distinct cell types that emerge, their dynamics, and their relationship to progenitors in the early embryo has been difficult to decipher because of the cellular heterogeneity inherent to differentiation. Here, we used a combination of bulk RNA-Seq, single cell RNA-Seq, and bioinformatics analyses to dissect the cell types that emerge during directed differentiation of mouse embryonic stem cells as embryoid bodies and we compared them to spatially and temporally resolved transcriptional profiles of early embryos. Our single cell analyses of the day 4 embryoid bodies revealed three populations which had retained related yet distinct pluripotent signatures that resemble the pre- or post-implantation epiblast, one population of presumptive neuroectoderm, one population of mesendoderm, and four populations of neural progenitors. By day 6, the neural progenitors predominated the embryoid bodies, but both a small population of pluripotent-like cells and an anterior mesoderm-like Brachyury-expressing population were present. By comparing the day 4 and day 6 populations, we identified candidate differentiation paths, transcription factors, and signaling pathways that mark the in vitro correlate of the transition from the mid-to-late primitive streak stage.
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影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
3.6
作者：
Avraham O;Hadas Y;Vald L;Zisman S;Schejter A;Visel A;Klar A
通讯作者：
Klar A
DOI：
10.1073/pnas.231396598
发表时间：
2001-11-06
影响因子：
11.1
作者：
Hemberger, M;Cross, JC;Himmelbauer, H
通讯作者：
Himmelbauer, H
影响因子：
11.8
作者：
Guo, Guoji;Huss, Mikael;Robson, Paul
通讯作者：
Robson, Paul
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz