ModEvoCell · Modelling cell type evolution in animals
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-04-01 → 2024-05-12
- EU contribution
- €160,932
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Modelling cell type evolution in animals
This project set out to explore the evolutionary dynamics of cell type change in the animal lineage (the Metazoa). Animals are built from an array of specialised cell types and tissues that constitute the physical and functional building blocks of their complex multicellular organisms. These cell types are complex phenotypes controlled by multiple biological phenomena—ontogeny, morphology, regulatory and transcriptional states, etc.—that are encoded by a single genome (that of the animal). Therefore, these phenomena are subject to the evolutionary process and can be studied from a functional genetic point of view — i.e., studying the patterns of conservation and divergence of the various genetic traits that determine cell phenotypes. I proposed to investigate the evolution of animal cell types in a comparative framework involving multiple species. The study of the cell type and transcriptomic programmes of various species along a spectrum of phylogenetic divergence times allowed me to outline a data-driven model of evolution that quantifies the influence of regulatory divergence on cell type evolution. As a biological model for this project, I selected multiple placozoan species. Placozoans are microscopic sea-dwelling animals with limited cell type diversity (thus enabling in-depth single-cell transcriptomic analysis at low cost) and highly conserved genomes (thus enabling straightforward and information-rich cross-species comparisons). Thus, they are ideal models for an initial study of cell type evolutionary modelling. In that regard, the three main aims of the project were: Aim 1 – Catalogue cell types, regulatory regions and gene regulatory networks across placozoans, using single-cell transcriptomics, regulatory profiling (ATAC-seq), and gene module modelling. Aim 2 – A cross-species comparative analysis of the determinants of cell type identity, using genetic and functional phylogenetic models. Aim 3 – Build models of cell type and regulatory evolution in placozoans, integrating information from Aims 1 and 2 in a unifying framework. This project was devised at a time when single-cell transcriptomic atlases from various species are becoming increasingly available. The ensuing deluge of data enables unprecedented large-scale comparisons and could revolutionise our understanding of cell behaviours in a way similar to the advances brought about by the advent of comparative genomics. Understanding how genetic variation relates to cell type innovation and conservation is central to this endeavour, and I thus sought to cover this gap.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- FUNDACIO CENTRE DE REGULACIO GENOMICA · BarcelonaCoordinatorSpain
Links
Data: CORDIS, © European Union