Mapping single-cell atlases throughout Metazoa unravels cell type evolution

Abstract

Comparing single-cell transcriptomic atlases from diverse organisms can elucidate the origins of cellular diversity and assist the annotation of new cell atlases. Yet, comparison between distant relatives is hindered by complex gene histories and diversifications in expression programs. Previously, we introduced the self-assembling manifold (SAM) algorithm to robustly reconstruct manifolds from single-cell data (Tarashansky et al., 2019). Here, we build on SAM to map cell atlas manifolds across species. This new method, SAMap, identifies homologous cell types with shared expression programs across distant species within phyla, even in complex examples where homologous tissues emerge from distinct germ layers. SAMap also finds many genes with more similar expression to their paralogs than their orthologs, suggesting paralog substitution may be more common in evolution than previously appreciated. Lastly, comparing species across animal phyla, spanning mouse to sponge, reveals ancient contractile and stem cell families, which may have arisen early in animal evolution.

Systematic reconstruction of cellular trajectories across mouse embryogenesis

“…We compared our cell-type alignments between zebrafish versus frog to a recent study 110 that also sought to align the same datasets. We could find consistent alignments for 35 of 46 pairs of cell types that they identified (Supplementary Table 29 ).…”

Multiple Origins of Neurons From Secretory Cells

“…This view does not prevent establishing evolutionary lineages of homologous cell types within particular taxonomical units such as classes, subclasses, orders, families, and genera. The cell-lineage-specific homologies across phyla are still a challenge (Tarashansky et al, 2020 ).…”

“…But, no criteria for cell-specific homologies across phyla have been established and experimentally validated. Some approaches are suggested (Tarashansky et al, 2020 ), but true homology can only be found with multiple cross-validated criteria, including identifying potential continuity of homologs tracing intermedial species. Here, the lack of required comparative data from “minor” phyla and classes is a significant bottleneck.…”

A Primer for Single-Cell Sequencing in Non-Model Organisms

“…By defining a set of homologous genes across species, cross-species comparison of gene expression can be achieved to study problems such as the expression pattern of core genes of the cells. For closely related species, commonly used methods such as STAR can be applied to identify a set of homologous genes across species; there are also programs such as SAMap [ 56 ] to build a homologous gene set between distant species that is usually a challenge.…”