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Early metazoan cell type diversity and the evolution of multicellular gene regulation


A hallmark of metazoan evolution is the emergence of genomic mechanisms that implement cell-type-specific functions. However, the evolution of metazoan cell types and their underlying gene regulatory programmes remains largely uncharacterized. Here, we use whole-organism single-cell RNA sequencing to map cell-type-specific transcription in Porifera (sponges), Ctenophora (comb jellies) and Placozoa species. We describe the repertoires of cell types in these non-bilaterian animals, uncovering diverse instances of previously unknown molecular signatures, such as multiple types of peptidergic cells in Placozoa. Analysis of the regulatory programmes of these cell types reveals variable levels of complexity. In placozoans and poriferans, sequence motifs in the promoters are predictive of cell-type-specific programmes. By contrast, the generation of a higher diversity of cell types in ctenophores is associated with lower specificity of promoter sequences and the existence of distal regulatory elements. Our findings demonstrate that metazoan cell types can be defined by networks of transcription factors and proximal promoters, and indicate that further genome regulatory complexity may be required for more diverse cell type repertoires.

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Fig. 1: Comparison of genomic features of early metazoans and phylogenetically related species.
Fig. 2: A. queenslandica adult and larval cell type atlases.
Fig. 3: M. leidyi and T. adhaerens cell type atlases.
Fig. 4: Phylogenetic patterns of cell-type-specific gene repertoires.
Fig. 5: Transcription factor regulatory programmes in A. queenslandica, M. leidyi and T. adhaerens.
Fig. 6: Regulatory sequence analysis in A. queenslandica, M. leidyi and T. adhaerens.


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We thank all members of the Tanay laboratory for comments and discussion, X. Grau-Bové for genome statistics in different species, A. Furu for help with M. leidyi, and H.-J. Osigus and B. Schierwater for providing T. adharens starting culture. Research in A.H.’s group was supported by the European Research Council Community’s Framework Program Horizon 2020 (2014–2020) ERC grant agreement 648861 and an NSF IRFP Postdoctoral Fellowship (1158629) to K.P. Research by B.M.D. is supported by the Australian Research Council. A.S.-P. was supported by an EMBO Long-Term Fellowship (ALTF 841-2014). Research in A.T.’s group was supported by the European Research Council Community’s Framework Program Horizon 2020 (2014–2020) ERC grant agreement 724824. A.T. is a Kimmel investigator.

Author information




A.S.-P. and A.T. conceived the project. K.P., A.H., B.M.D. and F.G. provided animal specimens and chromatin material. Z.M. and E.C. assisted with experimental setup and analysis tools. I.A. assisted with iChIP and MARS-seq setup and reagents. A.S.-P. performed the MARS-seq experiments. A.S.-P. and D.L.-A. performed the iChIP experiments. A.S.-P. and A.T. analysed the data and wrote the manuscript. All authors discussed and commented on the data.

Corresponding authors

Correspondence to Arnau Sebé-Pedrós or Amos Tanay.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary figures 1–8, Legends for Supplementary tables 1–7.

Reporting Summary


MetaCell guide.

Supplementary table 1

A. queenslandica, M. leidyi and T. adharens scRNA sequencing library statistics.

Supplementary table 2

A. queenslandica adult cell clusters enriched gene lists.

Supplementary table 3

A. queenslandica larva cell clusters enriched gene lists.

Supplementary table 4

M. leidyi cell clusters enriched gene lists.

Supplementary table 5

T. adhaerens cell clusters enriched gene lists.

Supplementary table 6

Taxon sampling employed in the orthoclustering analysis.

Supplementary table 7

A. queenslandica, M. leidyi and T. adharens de novo motifs.

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Sebé-Pedrós, A., Chomsky, E., Pang, K. et al. Early metazoan cell type diversity and the evolution of multicellular gene regulation. Nat Ecol Evol 2, 1176–1188 (2018).

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