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

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. | Dong et al. Genome Biology 2018 19 31 https doi.org 10.1186 s13059-018-1416-2 RESEARCH ARTICLE Open Access Single-cell RNA-seq analysis unveils a prevalent epithelial mesenchymal hybrid state during mouse organogenesis Ji Dong1 2 Yuqiong Hu1 2 3 Xiaoying Fan1 2 Xinglong Wu1 2 3 Yunuo Mao1 2 Boqiang Hu1 2 Hongshan Guo1 2 Lu Wen1 2 and Fuchou Tang1 2 3 Abstract Background 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. Results 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. Conclusions 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. Keywords Single-cell RNA-seq Organogenesis Interactions between mesenchyme and epithelium Epithelial mesenchymal hybrid state Background induced and specified 2 3 . Another important cellular During mammalian embryonic development organogen- mechanism characterizing embryonic development is esis is a crucial process leading to the .