Comprehensive single-cell transcriptome lineages of a proto-vertebrate (the sea squirt)

These GEITP pages, from time to time, highlight a particularly exciting breakthrough in developmental biology [see attached article and editorial]. Single-cell RNA-sequencing methods are revolutionizing our understanding of how cells are specified to become definitive tissues during development. Such studies allow elucidation of virtual lineages for select tissues, and provide detailed expression profiles for cell-types (e.g. pluripotent progenitor cells, which are capable of differentiating into any cell-type). However, a major limitation of previous studies has been the incomplete coverage of vertebrate embryos — owing to the large numbers of cells present in these embryos.

As one of the closest living relatives of vertebrates (animals having spines), the ascidian Ciona intestinalis (sea squirt) serves a critical role in understanding developmental and physiological processes that are comparable to — but far less complex than — those of vertebrates. In comparison to vertebrate embryos, sea squirt embryos are simple: gastrulating embryos (see Figure 1 of attached article, showing gastrula as the original ball of cells) are composed of only 100–200 cells, and swimming tadpoles contain ~2,500 cells.

Owing to these small numbers of cells, it is possible to obtain comprehensive coverage of every cell-type during development, including rare neuronal subtypes. Authors [see attached] extended insights into the regulatory ‘blueprint’ that spans the early phases of embryogenesis, by profiling the transcriptomes (i.e. ‘active gene’ transcripts that are transcribed into messenger RNA) of individual cells in sequentially staged Ciona embryos, from gastrulation at the 110-cell stage to the neurula and larval stages.

Authors determined single-cell transcriptomes for more than 90,000 cells that span the entirety of development — from the onset of gastrulation to swimming tadpoles — in the sea squirt. Authors used single-cell transcriptome trajectories to construct virtual cell-lineage maps and provisional gene networks for 41 neuronal subtypes that comprise the larval nervous system. Authors summarized several applications of these datasets, including annotating the synaptome of swimming tadpoles and tracing the evolutionary origin of cell types such as the vertebrate telencephalon (the most highly developed, and frontal, part of the forebrain, consisting chiefly of the cerebral hemispheres in vertebrates).

Nature 18 July 2019; 571: 349-354 & pp 333-334 (editorial)

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