Biology subjects

Todd, H.

Publications and source records attributed to Todd, H..

3 recordsLinked to original sources

bioRxiv2025

Development and Characterisation of Equine Gastric Organoids

The healthy equine stomach is of essential importance to equine digestive health and overall wellbeing. Diseases of the gastric mucosa such as gastric ulcers are highly prevalent in equids, particularly amongst racing thoroughbreds, and present a significant challenge to animal health and welfare. Despite this, there is currently no lab-based model capable of accurately representing the cellular diversity and cellular interactions within the equine gastric mucosa to aid in development of treatment options. We present here the first report of equine gastric organoids derived from glandular mucosa tissue. Through bulk RNA-sequencing and immunofluorescence we show these gastric organoids are representative of the tissue whilst retaining the individual gene-expression properties of the animal they were derived from. We also show these organoids are stable over multiple passages and can be differentiated towards different cell-types to upregulate protein and gene expression of specialised cell markers such as gastric foveolar cell associated mucin 5ac, gastrokine 1 & 2 and trefoil factor 2. This model establishes the first physiologically relevant in vitro model of the equine gastric epithelium, representing a significant opportunity for developing understanding and therapeutic treatments of gastric diseases in equids.

cell biology↗

bioRxiv2024

Pathophysiology of hypereosinophilia-associated heart disease

BackgroundCardiac complications in patients with hypereosinophilia cause significant morbidity and mortality. However, mechanisms of how eosinophilic inflammation causes heart damage are poorly understood. MethodsWe developed a model of hypereosinophilia-associated heart disease by challenging hypereosinophilic mice with peptide from the cardiac myosin heavy chain. Disease outcomes were measured by histology, immunohistochemistry, flow cytometry, and measurement of cells and biomarkers in peripheral blood. Eosinophil dependence was determined by using eosinophil-deficient mice ({Delta}dblGATA). Single cells from heart were subjected to single cell RNA sequencing to assess cell composition, subtypes and expression profiles. ResultsMice challenged with myocarditic and control peptide had peripheral blood leukocytosis, but only those challenged with myocarditic peptide had heart inflammation. Heart tissue was infiltrated by eosinophil-rich inflammatory infiltrates associated with cardiomyocyte damage. Disease penetrance and severity were dependent on the presence of eosinophils. Single cell RNA sequencing showed enrichment of myeloid cells, T-cells and granulocytes (neutrophils and eosinophils) in the myocarditic mice. Macrophages were M2 skewed, and eosinophils had an activated phenotype. Gene enrichment analysis identified several pathways potentially involved in pathophysiology of disease. ConclusionEosinophils are required for heart damage in hypereosinophilia-associated heart disease. Additionally, myeloid cells, granulocytes and T-cell cooperatively or independently participate in the pathogenesis of hypereosinophilia-associated heart disease.

immunology↗

bioRxiv2021

Non-Canonical Projections from Ventral CA1 and Subicular Complex to CA3 Augments the Feedforward Hippocampal Trisynaptic Pathway

The hippocampal formation is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the hippocampal formation, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral-genetic mapping techniques enhances our ability to determine the detailed complexity of hippocampal formation circuitry. In earlier work, we mapped a subiculum back-projection to CA1 prompted by the discovery of theta wave back-propagation from the subiculum to CA1 and CA3. We reason that this circuitry may represent multiple extended non-canonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant non-canonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1, perirhinal cortex, and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3. Together, our data provide a circuit foundation to explore novel functional roles contributed by these non-canonical hippocampal circuit connections to hippocampal dynamics and behavior.

neuroscience↗