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Cross-species single-cell transcriptomics and its applications in evolutionary and translational research https://doi.org/10.17863/CAM.107507 Keitley, Daniel Benito-Gutiérrez, Èlia Marioni, John Single-cell transcriptomics has emerged as a powerful technology to characterise gene expression within individual cells. Over the last 5 years, as the technology has matured, single-cell techniques have been used to profile cells in species across the tree of life. The availability of single-cell data from a rich diversity of species presents an opportunity to compare gene expression, cell types and developmental programmes across organisms and interpret these transcriptomic observations within a phylogenetic framework. This opens up new possibilities to study the evolution of cell types and infer molecular properties of organisms inaccessible to experimental research. In this thesis, I explore these two applications in the context of early mammalian development and vertebrate brain evolution. I first detail efforts to construct a single-cell atlas of rabbit gastrulation, which offers a new window into human embryogenesis and provides a resource for validating therapeutic targets, or observations from mice, in a non-rodent system. I then present three new approaches to visualise and compare single-cell transcriptomics data from multiple species. These methods overcome challenges of relating gene features and cell types, which may be applicable to contexts beyond the cross-species setting. Finally, I apply comparative single-cell analyses to trace networks of neural development across deuterostomes. This reveals a conserved molecular signature present in the sea urchin, amphioxus and zebrafish embryo and offers a template for future studies to compare vertebrate and invertebrate nervous systems with single-cell approaches. University of Cambridge 2023-09-07 Thesis Doctoral Doctor of Philosophy (PhD) eng Wellcome Trust PhD Studentship https://www.repository.cam.ac.uk/handle/1810/366669 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/889f4eec-37c9-4d30-a428-166e4b06b1be/download e9909b1f5052f747ff1ac52359000e8f https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/0c47225b-93f4-4bd7-a861-8339554d6d57/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ amphioxus comparative analysis cross-species cross-species scRNA-seq evo-devo evolution gastrulation rabbit scRNA-seq single-cell single-cell RNA-sequencing single-cell transcriptomics