Journal Article

Cell type atlas and lineage tree of a whole complex animal by single-cell transcriptomics

Rajewsky, Nikolaus, Plass, Mireya, Solana, Jordi, Obermayer, Benedikt, Misios, Aristotelis, Glažar, Petar, Wolf, F. Alexander, Kocks, Christine, Ayoub, Salah, Theis, Fabian J.

2018

Overview

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 Single-cell analysis reveals major planarian cell types, a differentiation tree, and genes for specific differentiation events. Flatworms of the species Schmidtea mediterranea are immortal—adult animals contain a large pool of pluripotent stem cells that continuously differentiate into all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterized gene expression changes during differentiation and discovered cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution.

• Publisher: The American Association for the Advancement of Science
• Subject: Active control / Algorithms / Animals / Biology / Cell lineage / Cells (biology) / Computation / Computer applications / Cytology / Developmental stages / Differentiation (biology) / Flatworms / Gene expression / Gene mapping / Gene sequencing / Genes / Individualized Instruction / Mapping / Mathematical models / Medical science / Metabolism / Molecular chains / Molecular modelling / Organs / Perturbation methods / Pluripotency / Progenitor cells / Progressions / Reconstruction / Regeneration / Ribonucleic acid / RNA / Schmidtea mediterranea / Stem cell transplantation / Stem cells / Trajectory analysis / Transcription / Turbellaria