Modelling cell type evolution in animals

Descrizione del progetto

Approfondimenti sull’evoluzione del tipo cellulare

Gli animali contengono una varietà di tipi di cellule con fenotipi e funzioni distinti. Sebbene queste cellule contengano lo stesso genoma, attributi epigenetici, regolatori e trascrizionali diversi le conferiscono questa notevole diversità fenotipica. Il progetto ModEvoCell, finanziato dall’UE, sta focalizzando la propria attenzione sull’evoluzione delle caratteristiche che definiscono la diversità cellulare. I ricercatori studieranno il trascrittoma e mapperanno le regioni regolatorie di diverse cellule di varie specie di placozoi attraverso la divergenza filogenetica. I risultati contribuiranno a generare un modello di evoluzione del tipo di cellula, facendo luce su come compaiono e si diversificano i diversi tipi di cellule.

Obiettivo

Cell types with distinct functions coexist and cooperate within a single animal, eventually contributing to the endless forms most beautiful that define the animal kingdom. These cell types are complex phenotypes defined by multiple traits—ontogeny, morphology, regulatory and transcriptional states, etc.—that are ultimately encoded by the same genome, and are thus subject to the evolutionary process. Therefore, to study the diversity of cell types from an evolutionary perspective we need to first understand the patterns of conservation and divergence in the various traits that determine cell phenotypes. Among these traits, gene regulation is uniquely amenable to be systematically catalogued and compared across species, and it is an ideal candidates to support a model of cell type evolution.

Here I propose to investigate the evolution of animal cell types in a multi-species comparative framework. I hypothesise that, by characterising the cell type and transcriptomic programmes of various species along a spectrum of phylogenetic divergence times, I will be able to infer a data-driven model to quantify the influence of regulatory divergence on cell type evolution. To that end, I will build cell type diversity atlases of six placozoan species and resolve their transcriptomic states at single-cell resolution using scRNA-seq, genome-wide profiling of regulatory regions (ATAC-seq and regulatory motif discovery), and gene regulatory network modelling. Placozoans are a uniquely well-suited model for this research: they have a strongly conserved yet profoundly simple bauplan, composed of few cell types, that can be fully resolve at the whole-organism level using single-cell transcriptomics. This taxon-rich survey across multiple species and cell types will allow me to address the fundamental question of how cell types emerge and diversify, and it will provide a theoretical basis to understand how regulatory divergence ultimately results in phenotypic innovation.