Periodic Reporting for period 3 - EvoCellMap (Tracing the origin and early evolution of animal cell type regulation with genomics and single-cell approaches)
Période du rapport: 2023-01-01 au 2024-06-30
Cell types are the fundamental units of animal multicellularity. Distinct cell types are established and maintained by specific gene regulatory networks (GRNs), as well as epigenomic mechanisms that mediate the asymmetric access to genetic information within each cell. This cell regulation results in complex metazoan functions and structures. However, cell types and their regulation have only been characterized in a few species. Therefore, the origin and evolution of animal cell types remain largely unexplored, and so remains the evolution of the underlying GRNs and epigenomic mechanisms.
In this project, we are developing a unified comparative framework to study cell type evolution and regulation from a multi-level and phylogenetic perspective. We focus on non-bilaterian metazoan lineages (Porifera, Ctenophora, Placozoa, and Cnidaria) as they can inform us about the evolutionary origins of metazoan genome regulation and of major cell types and their GRNs (e.g. neurons, secretory cells, stem cells, epithelial cells). More specifically, we integrate single-cell genomics and epigenomic profiling methods with advanced computational tools in order to: (1) investigate the origins of the animal regulatory genome; (2) characterize the diversity of cell type programs in non-bilaterian metazoans; and (3) model the structure and evolutionary dynamics of cell type-specific GRNs in these lineages.
This evolutionary systems biology approach provides a complementary angle to both phylogenetically-restricted single-cell analyses and traditional cross-species studies based on targeted marker genes. Therefore, our results will fill a large gap of knowledge in our understanding of the origin and diversification of animal cell type programs and epigenomic mechanisms. In a broader context, this research program will provide unprecedented insights into the fundamental question of how cell types and their defining regulatory networks evolve.
In this project, we are developing a unified comparative framework to study cell type evolution and regulation from a multi-level and phylogenetic perspective. We focus on non-bilaterian metazoan lineages (Porifera, Ctenophora, Placozoa, and Cnidaria) as they can inform us about the evolutionary origins of metazoan genome regulation and of major cell types and their GRNs (e.g. neurons, secretory cells, stem cells, epithelial cells). More specifically, we integrate single-cell genomics and epigenomic profiling methods with advanced computational tools in order to: (1) investigate the origins of the animal regulatory genome; (2) characterize the diversity of cell type programs in non-bilaterian metazoans; and (3) model the structure and evolutionary dynamics of cell type-specific GRNs in these lineages.
This evolutionary systems biology approach provides a complementary angle to both phylogenetically-restricted single-cell analyses and traditional cross-species studies based on targeted marker genes. Therefore, our results will fill a large gap of knowledge in our understanding of the origin and diversification of animal cell type programs and epigenomic mechanisms. In a broader context, this research program will provide unprecedented insights into the fundamental question of how cell types and their defining regulatory networks evolve.
We have started building cell type transcriptional atlases for diverse species, and we have developed tools to analyze and integrate these cell maps across species. The most recent example of such cell atlases is that of a very peculiar type of cnidarians: stony corals. Stony corals sustain the most biodiverse marine ecosystems on Earth: coral reefs. We samples three life stages of Stylophora pistillata (larva, settling polyps and adult colonies). We characterized the molecular pathways underlying key processes in the biology of corals: (i) we measured gene expression in both coral host cells and the dinoflagellate symbionts within, revealing the metabolic cross-talk and the regulatory pathways involved in coral symbiosis; (ii) we defined the developmental transcriptome of CaCO3 skeleton formation; (iii) we discovered the existence of cellular immunity in corals; and (iv) by comparing multiple cnidarian cell atlases, we traced the evolutionary history of coral cell type innovations.
Our work so far work expands single-cell sampling efforts to non-culturable species and also pioneers the application of these tools to study symbiosis in animals. Moreover, we have adapted diverse chromatin profiling methods to interrogate the genome regulatory mechanisms linked to this cell type diversity. In the second half of this project, we expect to move from descriptions of cell types in a single species and defined by gene expression profiles to cross-species comparisons of cell identities defined by gene regulatory networks.