Please use this identifier to cite or link to this item: http://theses.ncl.ac.uk/jspui/handle/10443/6326
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dc.contributor.authorOlabi, Bayanne-
dc.date.accessioned2024-10-18T11:37:01Z-
dc.date.available2024-10-18T11:37:01Z-
dc.date.issued2024-
dc.identifier.urihttp://hdl.handle.net/10443/6326-
dc.descriptionPh. D. Thesis.en_US
dc.description.abstractSkin tissue comprises distinct microanatomical regions across the epidermis, dermis and hair follicles that are pivotal for its physiological roles, including barrier protection and immunological surveillance. Within these regions, distinct cellular interactions occur between diverse cell types to govern skin structure and function across the lifespan, which can become perturbed in disease. Novel insights have recently been gained into skin pathophysiology from single cell RNA-sequencing (scRNA-seq) of adult healthy, psoriasis and eczema skin. However, single-cell data derived from dissociated tissue loses valuable information about gene expression in situ, which informs cellular communication and identity. The aims of this project were therefore to use spatial transcriptomics to profile adult skin samples from healthy, lesional and non-lesional psoriasis and eczema skin, and leverage a reference scRNA-seq dataset to map cell states across tissue sections. Comparative analyses of spatial data between healthy and disease conditions demonstrated widespread changes in the tissue location of immune and non-immune cells and revealed functional microanatomical cellular niches that become perturbed in psoriasis and eczema. Based on these findings, the concept of functional skin cellular microenvironments was then explored during skin and hair morphogenesis by annotating and spatially mapping scRNA-seq data from first and second trimester prenatal skin. The analyses revealed distinct cellular microenvironments and intercellular crosstalk supporting skin and hair follicle development. Integrating adult hair follicle and hair-bearing skin organoid datasets contextualised the differences with in vivo prenatal skin and provided support for congenital skin and hair disease modelling in vitro. Together, this spatially-resolved atlas of human skin in adulthood and during prenatal skin development has provided unprecedented microanatomical detail and insight into functional skin cell microenvironments. This has future applications for enhancing our understanding of skin and hair disease pathogenesis, identifying novel therapeutic targets, and facilitating tissue engineering for hair follicle and skin regeneration and transplantation.en_US
dc.description.sponsorshipWellcomeen_US
dc.language.isoenen_US
dc.publisherNewcastle Universityen_US
dc.titleFunctional skin microenvironments unravelled through single cell and spatial transcriptomic analysisen_US
dc.typeThesisen_US
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