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

• Published in: Genome Biology Vol. 19; no. 1; p. 31
• Main Authors: Dong, Ji, Hu, Yuqiong, Fan, Xiaoying, Wu, Xinglong, Mao, Yunuo, Hu, Boqiang, Guo, Hongshan, Wen, Lu, Tang, Fuchou
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14.03.2018; BMC
• Subjects: Bioinformatics; brain; carcinogenesis; Embryogenesis; Embryos; Epithelial cells; Epithelial/mesenchymal hybrid state; epithelium; Forebrain; Gene expression; Gene regulation; genome; heart; Hindbrain; hybrids; Interactions between mesenchyme and epithelium; Intestine; intestines; Liver; lungs; Mammals; Mesenchyme; mice; neurons; Organogenesis; Ribonucleic acid; RNA; sequence analysis; Single-cell RNA-seq; Skin; Stem cells; Studies; Transcription factors; transcriptome; Tumorigenesis; Interactions between mesenchyme and epithelium; Single-cell RNA-seq; Epithelial/mesenchymal hybrid state; Organogenesis
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-018-1416-2

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.