The Drosophila embryo at single-cell transcriptome resolution
Nikos Karaiskos1,*, Philipp Wahle2,*, Jonathan Alles1, Anastasiya Boltengagen1, Salah Ayoub1, Claudia Kipar2, Christine Kocks1, Nikolaus Rajewsky1,†, Robert P. Zinzen2,†
1Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
2Systems Biology of Neural Tissue Differentiation, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
↵†Corresponding author. Email: nikolaus.rajewsky@mdc-berlin.de (N.R.); robert.zinzen@mdc-berlin.de (R.P.Z.)
↵* These authors contributed equally to this work.
Science 31 Aug 2017: eaan3235
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 produce 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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