Evolutionary cell type mapping with single-cell genomics

Amos Tanay, Arnau Sebé-Pedrós

Research output: Contribution to journalArticlepeer-review


A fundamental characteristic of animal multicellularity is the spatial coexistence of functionally specialized cell types that are all encoded by a single genome sequence. Cell type transcriptional programs are deployed and maintained by regulatory mechanisms that control the asymmetric, differential access to genomic information in each cell. This genome regulation ultimately results in specific cellular phenotypes. However, the emergence, diversity, and evolutionary dynamics of animal cell types remain almost completely unexplored beyond a few species. Single-cell genomics is emerging as a powerful tool to build comprehensive catalogs of cell types and their associated gene regulatory programs in non-traditional model species. We review the current state of sampling efforts across the animal tree of life and challenges ahead for the comparative study of cell type programs. We also discuss how the phylogenetic integration of cell atlases can lead to the development of models of cell type evolution and a phylogenetic taxonomy of cells.
Cell types are the basic functional units of multicellular organisms. So far, cell taxonomies remain Linnaean.Single-cell transcriptomic methods enable the systematic characterization of cell diversity in understudied animal lineages. These data-driven cell catalogs should allow us to organize cell diversity into evolutionary classification schemes.Single-cell sampling bias and other technical limitations can severely constrain our ability to integrate cell atlases across species. It is important to advance towards general sampling strategies and data standards.Comparative analysis of cell type atlases uncovers transcriptional similarities across species, but are confounded by pleiotropy and non-independence of gene expression patterns, particularly at large phylogenetic distances.The interrogation of cell type regulatory programs in closely related species should enable the development of quantitative models of cell type evolution and to assess the (potentially incongruent) evolutionary histories of the different components of these programs.
Original languageEnglish
Pages (from-to)919-932
Number of pages14
JournalTrends in Genetics
Issue number10
StatePublished - Oct 2021


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