Research Article

The Drosophila embryo at single-cell transcriptome resolution

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Science  13 Oct 2017:
Vol. 358, Issue 6360, pp. 194-199
DOI: 10.1126/science.aan3235

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3D gene expression blueprint of the fly

When looking at populations of cells, features such as cell heterogeneity and localization are masked. However, single-cell sequencing reveals cellular heterogeneity and rare cell types. At the onset of gastrulation, the fly embryo consists of about 6000 cells with distinct gene expression profiles. Karaiskos et al. developed an algorithm to generate an interactive three-dimensional (3D) “virtual embryo,” with the expression of more than 8000 genes per cell measured for most cells (see the Perspective by Stadler and Eisen). The virtual embryo offers insights into developmental mechanisms—from local expression of regulators such as transcription factors and long noncoding RNAs to spatial modulation of signaling pathways.

Science, this issue p. 194; see also p. 172

Abstract

By the onset of morphogenesis, Drosophila embryos consist of about 6000 cells that express distinct gene combinations. Here, we used single-cell sequencing of precisely staged embryos and devised DistMap, a computational mapping strategy to reconstruct the embryo and to predict spatial gene expression approaching single-cell resolution. We produced a virtual embryo with about 8000 expressed genes per cell. Our interactive Drosophila Virtual Expression eXplorer (DVEX) database generates three-dimensional virtual in situ hybridizations and computes gene expression gradients. We used DVEX to uncover patterned expression of transcription factors and long noncoding RNAs, as well as signaling pathway components. Spatial regulation of Hippo signaling during early embryogenesis suggests a mechanism for establishing asynchronous cell proliferation. Our approach is suitable to generate transcriptomic blueprints for other complex tissues.

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