The embryo at single-cell transcriptome resolution.
Nikos Karaiskos, Philipp Wahle, Jonathan Alles, Anastasiya Boltengagen, Salah Ayoub, Claudia Kipar, Christine Kocks, Nikolaus Rajewsky, Robert P Zinzen
Author Information
Nikos Karaiskos: Systems 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. ORCID
Philipp Wahle: Systems Biology of Neural Tissue Differentiation, BIMSB, MDC, 13125 Berlin, Germany. ORCID
Jonathan Alles: Systems 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.
Anastasiya Boltengagen: Systems 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. ORCID
Salah Ayoub: Systems 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. ORCID
Claudia Kipar: Systems Biology of Neural Tissue Differentiation, BIMSB, MDC, 13125 Berlin, Germany. ORCID
Christine Kocks: Systems 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. ORCID
Nikolaus Rajewsky: Systems 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. nikolaus.rajewsky@mdc-berlin.de robert.zinzen@mdc-berlin.de. ORCID
Robert P Zinzen: Systems Biology of Neural Tissue Differentiation, BIMSB, MDC, 13125 Berlin, Germany. nikolaus.rajewsky@mdc-berlin.de robert.zinzen@mdc-berlin.de. ORCID
By the onset of morphogenesis, 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 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.
