Modeling cell type evolution using single-cell and chromatin profiling approaches
Single-cell genomics methods have revolutionized the study of gene expression and regulation at the cell type level. Generating single-cell atlases for species at key phylogenetic positions of the animal tree of life (e.g.. early branching non-bilaterian animals) informs us not only about the biolog...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/690731 |
| Acceso en línea: | http://hdl.handle.net/10803/690731 |
| Access Level: | acceso abierto |
| Palabra clave: | Evolution Genomics Animal diversity Gene regulation Transcriptomics Evolució Genòmica Diversitat animal Regulació gènica Transcriptòmica 575 |
| Sumario: | Single-cell genomics methods have revolutionized the study of gene expression and regulation at the cell type level. Generating single-cell atlases for species at key phylogenetic positions of the animal tree of life (e.g.. early branching non-bilaterian animals) informs us not only about the biology of these understudied groups of organisms, but also enable comparative studies of cell type transcriptomic programs. This is the first step towards inferring the evolutionary trajectories of major animal cell types. In this context, the first part of my thesis describes the first single cell atlas of a stony coral, Stylophora pistillata, and the novel insights we gained from it. We also compared cell type transcriptomes of Stylophora to three other species in the Cnidaria phylum, and identified conserved expression programs and convergent mobilization of similar molecular pathways in potentially homologous cell types across species. However, because transcriptome similarities are confounded by pleiotropy and non-independence of gene expression programs, they do not always represent true cell type homologies. To infer more accurate cell type phylogenetic relationships we need to also compare their gene regulatory programs. The second part of my thesis focuses on detailed regulatory characterization of cell type programs in cnidarian Nematostella vectensis. We describe genome-wide regulatory logic of Nematostella, and characterize cell types by modular deployment of transcription factors (TFs) and gene regulatory networks (GRNs) in which they are involved. Together, the work presented in this thesis exemplifies the ways in which single cell approaches can be used to advance our understanding of cell type diversity, development, and evolution. |
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