Cross-species single-cell transcriptomics and its applications in evolutionary and translational research

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.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2023

Author dc:creator

• Keitley, Daniel

Advisors dc:contributor.advisor

• Benito-Gutiérrez, Èlia
• Marioni, John

• 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

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/0c47225b-93f4-4bd7-a861-8339554d6d57/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.107507

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/366669