Christine Kocks

Cutting out circular RNAs Circular RNAs are widespread, but their functions have been controversial. Piwecka et al. used CRISPR-Cas9 technology to remove the locus encoding the circular RNA Cdr1as from the mouse genome. Single-cell electrophysiological measurements in excitatory neurons revealed an increase in spontaneous vesicle release from the knockout mice and depression in the synaptic response with two consecutive stimuli, indicating that Cdr1as deficiency leads to dysfunction of excitatory synaptic transmission. Small RNA sequencing of several major regions of the brain showed that expression of two microRNAs, miR-7 and miR-671, that bind to Cdr1as decreased and increased, respectively. These results, along with expression analyses, suggest that neuronal Cdr1as stabilizes or transports miR-7, which in turn represses genes that are early responders to different stimuli. Science , this issue p. eaam8526

Mapping the planarian transcriptome A cell type's transcriptome defines the active genes that control its biology. Two groups used single-cell RNA sequencing to define the transcriptomes for essentially all cell types of a complete animal, the regenerative planarian Schmidtea mediterranea. Because pluripotent stem cells constantly differentiate to rejuvenate any part of the body of this species, all developmental lineages are active in adult animals. Fincher et al. determined the transcriptomes for most, if not all, planarian cell types, including some that were previously unknown. They also identified transition states and genes governing positional information. Plass et al. used single-cell transcriptomics and computational algorithms to reconstruct a lineage tree capturing the developmental progressions from stem to differentiated cells. They could then predict gene programs that are specifically turned on and off along the tree, and they used this approach to study how the cell types behaved during regeneration. These whole-animal transcriptome “atlases” are a powerful way to study metazoan biology. Science , this issue p. eaaq1736 , p. eaaq1723

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