Biology subjects

Teasdale, M. D.

Publications and source records attributed to Teasdale, M. D..

4 recordsLinked to original sources

bioRxiv2026

Transient Vascular Cell Integration and Intrinsic Media-Stimulated Endothelial Activation Reveal Diabetic Retinopathy Signatures in Human Retinal Organoids

Retinal organoids (ROs) model human retinogenesis but remain avascular and lack immune components, limiting their utility for studying vascular retinopathies. We generated vascular organoids (VOrs) from human pluripotent stem cells and evaluated their integration into developing ROs. Dissociated VOr cells (day 12 or day 30) were seeded onto 2D retinal neuroepithelium before 3D transition, followed by long-term culture to day 210. VOr derived cells migrated into ROs and transiently persisted. V30 ROs preserved retinal lamination, major neuronal subtypes and light evoked retinal ganglion cell responses comparable to non vascularised controls, whereas media-only ROs cultured in proangiogenic conditions showed structural disorganisation and reduced neuronal survival. Single-cell RNA sequencing revealed an endogenous, inflammatory endothelial-like population with partial endothelial-to-mesenchymal features and a perivascular fibroblast-like cluster in pro-angiogenic media only RO controls. The endothelial-like cell cluster was significantly enriched for genes upregulated in human retinal endothelial cells exposed to high glucose, indicating a diabetic retinopathy like transcriptional state. Microglia like and border associated macrophage populations were present across all conditions, with developmental shifts in morphology and marker expression. Our findings define conditions under which vascular cells can be incorporated into human ROs without disrupting retinal architecture, while uncovering an intrinsic capacity for inflammatory endothelial activation that partially recapitulates diabetic retinopathy. This work advances the engineering of vascularised, immunocompetent retinal models and highlights endogenous vascular immune programmes that must be considered when modelling retinal disease in vitro.

neuroscience↗

bioRxiv2026

3,500 years of sheeppox virus evolution inferred from archaeological and codicological genomes

Sheeppox virus (SPPV) is a major livestock pathogen causing economic hardship through reduced production and death of vulnerable sheep, with written descriptions of sheeppox-like disease recorded since antiquity. We report 21 novel ancient SPPV genomes spanning the Eurasian steppe Bronze Age ([~]1,700 BCE) to the Early Modern period in Western Europe, including multiple genomes obtained from medieval parchment. We estimate that major capripoxvirus lineages diverged [~]11,500-3,700 years ago, overlapping known translocations and bio-cultural developments in sheep. Our dataset supports SPPV diverging first within the lineage leading to goatpox virus and lumpy skin disease virus, and that known gene inactivation events within SPPV and goatpox virus occur in our earliest SPPV genomes. These findings reveal that the food security of Eurasian communities have been threatened by sheeppox for over 3,700 years, and provide new insights to the genomic evolution and potential host adaptation of sheeppox virus. TeaserAncient viral genomes from manuscripts and teeth illuminate the evolutionary history of sheeppox virus.

genetics↗

bioRxiv2021

Exceptional ancient DNA preservation and fibre remains of a Sasanian saltmine sheep mummy in Chehrabad, Iran

Mummified remains have long attracted interest as a potential source of ancient DNA. However, mummification is a rare process that requires an anhydrous environment to rapidly dehydrate and preserve tissue before complete decomposition occurs. We present the whole genome sequences of a [~]1600 year old naturally mummified sheep recovered from Chehr[a]b[a]d, a salt mine in northwestern Iran. Comparative analyses of published ancient sequences revealed remarkable DNA integrity of this mummy. Hallmarks of postmortem damage, fragmentation and hydrolytic deamination, are substantially reduced, likely due to the high-salinity of this taphonomic environment. Metagenomic analyses reflect the profound influence of high salt content on decomposition; its microbial profile is predominated by halophilic archaea and bacteria, possibly contributing to the preservation of this sample. Applying population genomic analyses we find consistent clustering of this sheep with Southwest Asian modern breeds, suggesting ancestry continuity. Genotyping of a locus influencing the woolly phenotype showed the existence of an ancestral "hairy" allele in this sheep, consistent with hair fibre imaging, further elucidating Sasanian-period animal husbandry.

genomics↗

bioRxiv2017

The York Gospels: a one thousand year biological palimpsest

Medieval manuscripts, carefully curated and conserved, represent not only an irreplaceable documentary record but also a remarkable reservoir of biological information. Palaeographic and codicological investigation can often locate and date these documents with remarkable precision. The York Gospels (York Minster Ms. Add. 1) is one such codex, one of only a small collection of pre-conquest Gospel books to have survived the Reformation. By extending the non-invasive triboelectric (eraser-based) sampling technique eZooMS, to include the analysis of DNA we report a cost effective and simple-to-use biomolecular sampling technique. We apply this combined methodology to document for the first time a rich palimpsest of biological information contained within the York Gospels, which has accumulated over the 1,000 year lifespan of this cherished object that remains an active participant in the life of York Minster. This biological data provides insights into the decisions made in the selection of materials, the construction of the codex and the use history of the object.

genomics↗