Description

The Drosophila Embryo at Single Cell Transcriptome Resolution

Nikos Karaiskos*^,1, Philipp Wahle*^,2, Jonathan Alles¹, Anastasiya Boltengagen¹ , Salah Ayoub¹, Claudia Kipar², Christine Kocks¹, Nikolaus Rajewsky^$,1, Robert P. Zinzen^$,2

¹Systems Biology of Gene Regulatory Elements; 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

*Contributed equally

^$Corresponding authors

Drosophila is a premier model system for understanding the molecular mechanisms of development. By the onset of morphogenesis, ~6000 cells express distinct gene combinations according to embryonic position. Despite extensive mRNA in situ screens, combinatorial gene expression within individual cells is largely unknown. Therefore, it is difficult to comprehensively identify the coding and non-coding transcripts that drive patterning and to decipher the molecular basis of cellular identity. Here, we single-cell sequence precisely staged embryos, measuring >3100 genes per cell. We produce a ‘transcriptomic blueprint’ of development – a virtual embryo where 3D locations of sequenced cells are confidently identified. Our “Drosophila-Virtual-Expression-eXplorer” performs virtual in situ hybridizations and computes expression gradients. Using DVEX, we predict spatial expression and discover patterned lncRNAs. DEVX is sensitive enough to detect subtle evolutionary changes in expression patterns between Drosophila species. We believe DVEX is a prototype for powerful single cell studies in complex tissues.