Single-cell RNA-seq analysis unveils a prevalent epithelial/mesenchymal hybrid state during mouse organogenesis.

Single-cell RNA-seq analysis unveils a prevalent epithelial/mesenchymal hybrid state during mouse organogenesis.
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DOI:
10.1186/s13059-018-1416-2
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发表时间:
2018-03-14
期刊:
影响因子:
12.3
通讯作者:
Tang F
Tang F
中科院分区:
生物学1区
文献类型:
--
作者:
Dong J;Hu Y;Fan X;Wu X;Mao Y;Hu B;Guo H;Wen L;Tang F

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在哺乳动物胚胎发育过程中,器官发生对于器官的正常形成至关重要。然而,不同器官之间的相似性和共同特征以及在单细胞分辨率下此过程中的细胞异质性仍然难以捉摸。我们对E9.5至E11.5小鼠胚胎的8个器官和组织(即前脑、后脑、皮肤、心脏、体节、肺、肝和肠)的1916个单个细胞进行单细胞RNA测序分析。基于调节活性而不是表达模式,分析的所有细胞可以很好地分为四个主要组,具有上皮、中胚层、造血和神经元身份。对于同一类群内的不同器官,揭示并重构了它们的特征和发育路径的异同。我们确定了上皮细胞和间充质细胞之间的相互作用,并检测上皮细胞与普遍的间充质功能在器官形成过程中,这是类似的中间上皮/间充质细胞在肿瘤发生的功能。在我们的研究中,在单细胞分辨率下的全面转录组为未来管理哺乳动物器官发生的基因调控网络的机制研究铺平了道路。本文的在线版本(10.1186/s13059-018-1416-2)包含补充材料,可供授权用户使用。
Organogenesis is crucial for proper organ formation during mammalian embryonic development. However, the similarities and shared features between different organs and the cellular heterogeneity during this process at single-cell resolution remain elusive. We perform single-cell RNA sequencing analysis of 1916 individual cells from eight organs and tissues of E9.5 to E11.5 mouse embryos, namely, the forebrain, hindbrain, skin, heart, somite, lung, liver, and intestine. Based on the regulatory activities rather than the expression patterns, all cells analyzed can be well classified into four major groups with epithelial, mesodermal, hematopoietic, and neuronal identities. For different organs within the same group, the similarities and differences of their features and developmental paths are revealed and reconstructed. We identify mutual interactions between epithelial and mesenchymal cells and detect epithelial cells with prevalent mesenchymal features during organogenesis, which are similar to the features of intermediate epithelial/mesenchymal cells during tumorigenesis. The comprehensive transcriptome at single-cell resolution profiled in our study paves the way for future mechanistic studies of the gene-regulatory networks governing mammalian organogenesis. The online version of this article (10.1186/s13059-018-1416-2) contains supplementary material, which is available to authorized users.
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